Tag Archives: Rashida Bakait

Dr. Mohammad Rehan: Delhi’s Jamia Alumnus Working On New Biology-Oriented Methodology Towards Drug Discovery

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NEW DELHI :

Dr. Mohammad Rehan

This is the twelfth part of the series called “Scientist Says”, where we bring for our readers the significant research works of young scientists.

Dr. Mohammad Rehan completed his M.Sc. in Organic Chemistry (2010) from Jamia Millia Islamia University, New Delhi. Dr. Rehan started his doctoral studies at Indian Institute of Science Education and Research (IISER) Bhopal in 2011 with Prof. Prasanta Ghorai. During his doctoral studies, he worked on transition-metal catalyzed and transition metal-free synthesis of heterocycles & carbocyclic molecules. In 2017, he obtained his Ph.D. in chemistry from IISER, Bhopal, India. He joined as a postdoctoral research fellow in the group of Prof. H. Waldmann Max Planck Institute of Molecular Physiology, Dortmund, Germany, in May 2018 and worked till January 2021. He worked with the Group Leader Dr. Kamal Kumar, in the group of Prof. Waldmann, on asymmetric hetero-Diels–Alder reactions leading to biologically intriguing small molecules. He shares his research works with Rashida Bakait of India Tomorrow. Here are the excerpts of the interview.

Q. Please briefly explain your research.

Ans. My initial research was based on the development of synthetic methodology towards the synthesis of heterocyclic molecules and carbocyclic molecules. The purpose of developing a new synthetic methodology for the synthesis of heterocyclic molecules is that most marketed drugs contain heterocyclic fragments. Heteroatom’s (such as nitrogen, oxygen and sulfur) as well as heterocyclic scaffolds are often present as a key structural unit in several active pharmaceuticals natural products. Heterocyclic scaffolds are frequently present molecules in medicinal chemistry and among all such heteroclic molecules, nitrogen containing heterocyclic molecules are of great importance to medical science. Since nitrogen containing heterocyclic molecules are abundant in nature, existing as key units in several natural products, for examples, antibiotics, hormones and in vitamins. Nitrogen-containing natural products and some alkaloids compounds, showing various biological activities, several of them are even prescribed drugs such as serotonin, thiamine, which are called vitamin B1, papaverine, coniine, caffeine, nicotine, atropine, notorious morphine, and codeine. Statistically, more than 85% of all biologically active compounds contain heterocyclic moiety. These facts disclose and emphasize heterocyclic fragments play a central role in modern drug design and drug discovery. 

At IISER-Bhopal, my doctoral research began with the development of a new synthetic method for the synthesis of heterocyclic molecules and their application towards the synthesis of biologically active compounds. It was divided into two section: 1st section (1) transition-metal catalyzed synthesis of heterocyclic compounds (such as synthesis of 2-benzyl indole and 2-benzyl benzofuran derivatives) here the developed method was used towards the synthesis of melatonin receptor, anti-tumor and hypocholesterolemic agent, cytotoxic and mTOR signaling agent. In the second section (2) (a) transition-metal free synthesis of heterocyclic (such as derivatives of quinoline derivatives) with this develop methodology I have successfully synthesized 2-styrylquinolines (which shows combined therapeutic and diagnostic activities against Alzheimer’s and prion diseases). The 2- styrylquinolines is a vital scaffold and having considerable biological significance.

Besides the above-mentioned research, my research focus as a postdoctoral research fellow at Planck Institute of Molecular Physiology, Dortmund, Germany, was based on (a) asymmetric hetero-Diels–Alder reactions leading to biologically intriguing small molecules (here I have developed a synthetic methodology that enabled us to identify a new biological annotation to piperidinoyl spirooxindoles, which were known to exhibit inhibition of p53-MDM2 interaction. This work also demonstrates how important it is to develop methods for various possible stereoisomers of a desired product with stereogenic centers), and (b) synthesis of bio-inspired Pseudo-natural products (PNPs).

 Q. What was the objective of your research?

Ans. During my doctoral studies, I have gained immense experience in the development of new synthetic methodology. So I decided to extend my expertise towards drug discovery. It is only possible when there is a combination of chemistry and biology. I was looking for the research team where chemistry and biology work is going simultaneously, then only you can understand the real significance of the developed methodology for synthetic molecules. The scientific discipline of chemical biology is spanning the fields of chemistry and biology. It involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry to the study and manipulation of biological systems. When I joined the Prof. Waldmann research group (Prof. Waldmann is one of the renowned names in the field of chemical biology all over the world in academia and the pharmaceuticals industry) at MPI-Dortmund, my interest has developed to design and synthesize the Psuedo natural product based Molecular library towards the drug discovery. The synthesis of spiro-oxindole scaffold is present in various biologically intriguing natural products endowed with different biological activities. For example, Spirotryprostatin is isolated from the fermentation broth of A. fumigatus and shows antimitotic activity. Another natural product with spiro-oxindole core is Welwitindolinone which is isolated from H. welwitschii and reverses the effect of P-glycoprotein mediated multiple-drug-resistance. There are also various synthetic examples known where spiro-oxindoles show therapeutic effects, for instance, the antimalarial NITD609. An interesting subgroup of this class is the piperidinoyl-spirooxindole which consists of up to four consecutive chiral centers and up to three all-carbon-quaternary centers. Synthetic derivatives of this compound class appear to be promising anticancer agents. They inhibit the protein-protein interaction between the tumor suppressor p53 and MDM2. However, their potential in modulating other biological functions is not yet explored. 

Till date, there are some enantioselective HDA reactions reported with great control over their stereo chemical courses. They are applied for the total synthesis of natural products and used in the synthesis of small molecules. Our aim was to develop asymmetric access to 3,3’-piperidinoyl-spirooxindoles employing a catalytic HDA reaction with a 2-azabutadiene.

Q. Please mention some of the new findings of your research?

 Ans.The aim of chemical biology research is to get deeper insights into various known as well as novel biological processes by using chemical tools and techniques. An approach that is often chosen to accomplish this is to perturb a biological process that can be achieved with genetic approaches like gene silencing. The application of small molecules and the term small molecule is widely used and usually defines a molecular entity with a molecular weight under 1000 g/mol. Some of the important features of small molecules are their physicochemical properties like their permeability and solubility to penetrate the cell membrane and diffuse to their biological target in cell-based screenings. These properties are mainly influenced by molecular weight, lipophilicity, and the number of hydrogen bond donors and acceptors. So the design and development of synthetically small molecular libraries are very important in modern drug discovery.

Q What kind of challenges did you face?

Ans. Research is a lengthy process, so one must be self- motivated and should have a deep interest in the respective research areas. It will never be a cakewalk, your success will come after failure. Honestly, failure takes you towards success as you come to know various techniques and methods that might lead to failure. When I started my research for the development of a new synthetic methodology in chemistry I have faced similar problems.

Q. When did you begin and complete your research?

Ans. I started working as a doctoral researcher in August 2011 and successfully completed my Ph.D. degree in 2017. Then, I worked as a postdoctoral research fellow from May 2018 to January 2021 at Max Planck Institute of Molecular Physiology Dortmund Germany in the field of chemical biology. After the completion of my first post-doc, I took some break from my research work writing some reviews and research projects, now I want to start my own research group or would like to join the pharmaceutical industry to learn more about drug discovery.

 Q. Any scholarships or awards for research?

Ans. For my doctoral studies, I received a fellowship from MHRD-CSIR-UGC for 5 years. During my postdoctoral research, I received Max Planck Institute-Gesellschaft Germany Postdoctoral fellowship for the Postdoctoral research in Max-Planck Institute of Molecular Physiology Dortmund Germany.

Q. How do you think your research would be beneficial to the industry or society?

Ans. Several decades of research in various fields by the scientific community have led us to where we human beings are today: a civilized society with the knowledge and instruments to move forward. I believe that the synthetic methodology which I have developed during my doctoral studies in the area of organic chemistry and the research work during my postdoc will be helpful for the pharmaceuticals industry. By using such synthetic methodology the pharmaceuticals industry can develop new drugs. In the modern drug discovery we need to make an economically, environmentally sustainable and easily accessible method to provide the drugs in the market for the benefit the society.

 Q. Any new research you are planning to work on now?

Ans. Now , I would like to expand my research area on biocatalyst to develop new chemical transformation towards the drug discovery. Biocatalysis refers to the use of living systems or their parts to speed up (catalyze) chemical reactions. In biocatalytic processes, natural catalysts, such as enzymes, perform chemical transformations on organic compounds. In a class of catalysts of biocatalyst enzymes are accountable for the smooth transformation and enhancement of the rate of many crucial biochemical reactions in plants and animals. Nature is making biologically active compounds in plants via enzyme catalysis process from a longer time. The importance of enzyme catalyst is due to its efficiency, as a single molecule of the enzyme catalyst can convert up to a million of reactant molecules into the products in few seconds. Recent advances in the field of drug discovery helps the chemist to understand the structure and functional activities of enzymes, which have in turn led to an increase in their stability, activity, sustainability, and substrate specificity. At present, there are hundreds of different biocatalytic action that have been carried out in many pharmaceuticals, chemical, food, and agro-based industries (biocatalysis Tyler Johannes). 

Q. Please give few tips and suggestions for the budding scientists.

Ans. Doctoral research sometimes can be highly frustrating. At that time researcher should try to develop his own self-confidence and self-belief. Seek positive feedback and acknowledge your achievements. If your lack of determination is actively affecting your strength to work then seek consultation and professional help. Time management is very crucial. If you are not executing your goals on time, then plan properly again. And in the end don’t fear failure you can learn more from your failures than achievements. Failure can bring a positive change in your personal and professional life. Never take it personally, remember that you are receiving training to be a scientist. Try to understand the expectations of your supervisor.

Finally, you may need to explain your busy schedule during your research work to your family and friends. They may not understand the magnitude of research studies. You shouldn’t be nervous and don’t try to reject any opportunity to get-together. Remember one thing that discussing your research work with a layman can help to brush up it and it will further boost your motivation.

source: http://www.indiatomorrow.net / India Tomorrow / Home> Education> Featured / by Rashida Bakait, India Tomorrow /June 15th, 2021

Dr. Kausar Raza : Finding A New And Safe Method To Treat Cancer

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INDIA / California, USA :

Dr. Kausar Raza.

This is the seventh part of the series called `Scientist Says’ where we bring for our readers the significant and commendable research works of young scientists.

Dr. Mohammed Kausar Raza completed his M.Sc. in Inorganic Chemistry from Jamia Millia Islamia, Delhi and began his Ph.D. in the year 2015 with Prof. Akhil Chakravarthy lab, Inorganic and Physical Chemistry Dept., IISc, Bangalore. After completing his Ph.D in the year October 2019, he joined California Institute of Technology (Caltech) in the United States as a postdoctoral research fellow in January 2020. He shares his significant research works with Rashida Bakait of India Tomorrow. Here are the excerpts of the interview.

Q. Please give a brief explanation of your research.

Ans. My research interest mainly focuses on to locate the lesions with the help of [4Fe4S] cluster and their treatment using Pt-based anticancer agents. The research area is divided into two parts: (i) Investigating the chemical role of [4fe4S] cluster in eukaryotic proteins through electrochemical and biochemical studies. (ii) Use of Pt-based complexes for chemo phototherapeutic treatment of cancer.

Cancer is considered as one the deadliest diseases which has been outspreaded in various parts of the human body. Various methodologies have been implemented till date to fight against the proliferation of cancerous cells, namely, Chemotherapy (mainly Pt-based anticancer drugs), Photodynamic Therapy (which involves photosensitizer, light, molecular oxygen), etc. To fill the pitfalls of the conventional chemotherapeutic and photodynamic therapeutic drugs including the NER machinery and less tissue penetration respectively, during my PhD research at Indian Institute of Science, Bangalore, I combined these two well known modalities, i.e.; chemotherapy and photodynamic therapy (PDT) by tuning the structural properties of Pt-based complexes to kill the cancer cells selectively. The idea was to develop the series of conjugates bearing the structural framework as of the conventional chemotherapeutic anticancer drug, cisplatin and BODIPY dyes for PDT activity. In photodynamic therapy, the growth of cancer cells can be terminated in the presence of light which generates ROS (reactive oxygen species) capable of cleaving the DNA of the tumor cells and in turn causing the cell death. The cell imaging is beneficial to track the anti-cancer drug inside the body. The combination of the Pt metal which encrusted the path for DNA cross-linking and the BODIPY motif attached which aided in cell imaging and killing of cancer cells in the presence of light, comes out as a new scope to design the more efficient photodynamic chemotherapeutic anticancer agents.

Earlier in my PhD, I have made efforts to treat the cancer, now I am exploring my research to detect the lesions through DNA mediated charge transport chemistry. It focuses on assessing the functional role of iron sulfur [4Fe-4S] in eukaryotic DNA replicative and repair proteins. We perform the electrochemical investigation to detect the tumor/disordered sites using DNA mediated electron transfer.

Q. When did you begin and complete your research?

Ans. My research started with my master dissertation work in the year 2014. I started working as a PhD researcher in the January 2015 and successfully submitted my thesis in Oct. 2019. Now, I have been doing research as a postdoctoral fellow in the field of biochemistry since January 2020.

Q. What was the objective of your research?

Ans. Since a variety of anticancer drugs are known to treat numerous kinds of cancers, namely colorectal cancer, breast cancer, oral cancer, and lung cancer etc. My aim was to design and synthesize a drug in such a way which is highly selective towards killing the cancer cells without harming the normal living cells. We intended to approach a dual action mechanism of platinum based anticancer drugs for real time tracking and selective cancer cell death.

Q. What were the findings of your research?

Ans. We prepared a series of mono-functional Pt-based complexes capable of binding with DNA for the treatment against cancer. We have mainly designed the mitochondrial targeting anticancer drugs, as mitochondria is known as the powerhouse of the cell and it lack NER machinery. Major outcome of our studies is in the form of a indigenously synthesized prodrug which have 100-fold better anticancer activity than FDA approved Photofrin drug. Moreover, this drug can be tracked inside the cell which is not the case with any of the FDA approved platinum based anticancer drugs. We have conducted the in-vivo anticancer studies of these drugs in the living mice models using photodynamic chemotherapeutic dual action mechanism and obtained promising results which is turned out to be a patent in this emerging field. This work was done with the collaboration in the department of biological sciences at IISc.

Q. What was the conclusion of your research?

Ans. My work presents a thorough investigation on the Pt-based anticancer drugs derived from cisplatin motif. Appendment of BODIPY moieties as florescent probes aided in cell imaging and production of ROS to kill the cancer cells in presence of light. The in-depth photophysical investigation of our Pt based complexes revealed their properties to absorb visible light and made them suitable for real time tracking. This study provides further scope for combinatorial research that includes photodynamic therapy and DNA cross linking ability of the monofunctional Pt (II) drugs (chemotherapy) against cancer. Finally, the in vivo assay results on mice showed significant arrest of tumor growth and its shrinkage in size thus giving new insights in the chemistry of platinum-based PDT agents.

Q. What kind of challenges did you face?

Ans. In my masters, I have pursued a research project in coordination chemistry. I have learned various synthetic procedures to synthesize a variety of transition metal complexes and carried out an in-depth characterization using various spectroscopic techniques. Then I joined a bioinorganic chemistry lab, where the challenge was to design the metal complexes with a sharp focus on its pharmacology (pharmacokinetics) by implementing a cost-effective methodology. Also, the fluorophore motifs incorporated in the structure must have the significant absorption and emission photophysical properties which can aid the drug in penetrating deep inside the body. It was achieved after studying the UV-Vis properties of the drugs. Developing a drug performing a dual action mechanism in treating cancer cells was itself a challenge. Furthermore, I joined a biochemistry lab at Caltech, moving from bioinorganic to biochemistry was another major challenge, where I had to learn the new techniques and methods prior to performing the experiments and analyzing the outcomes.

Q. Any scholarships or awards for research?

Ans. As the recognition of my doctoral work, I received the prestigious Carl Storm International Diversity (CSID) fellowship for Gordon Research Conference (GRC), Metal in Medicine, USA. I am also a recipient of “Government of India International Travel Research Award (DST), CSIR Travel Research Award, ICMR Travel Research Award, SBIC Student Travel Grants for ICBIC-19 in Interlaken, Switzerland. I received fellowship from MHRD and CSIR for the five year during my Ph.D.  

Q. How do you think your research would be beneficial to the society or industry?

Ans. Cancer counts among the second deadliest diseases in the world. Among all types of cancer, about 30% of India’s affected population accounts for oral cancer only. Among the various therapies established for cancer treatment, photodynamic therapy is well known for the treatment of oral cancer. My research on Pt based drugs will provide a new insight and scope to combine the two therapies and kill the tumor with notable potency. Our mice model demonstrated an excellent efficacy of our drug inside the living being. These new findings can lead to investigate the drug-tumor interaction inside the human body. Implementation of our Pt based prodrugs will provide a new way to treat the cancer. Moreover, commercializing these drugs may reduce the cost of treatment. In addition, it’s manufacturing at industrial level will increase the employment for several educated and skilled people in our country.

Q. Any new research you are working on now?

Ans. Currently, I am working on the DNA mediated charge (electron) transfer chemistry. My aim is to investigate the rapid communication among DNA-processing proteins for repairment through DNA-mediated redox signaling. These DNA-processing enzymes bear an iron-sulfur [4Fe4S] cluster which performs common redox switch on binding with DNA and gives rise to DNA-charge transport chemistry. It mainly focuses on the electrochemical investigation of the chemical role of the [4Fe4S] cluster in eukaryotic DNA primase and the polymerase.  Importantly, electrochemistry on the DNA-modified electrodes facilitates reaction under aqueous, physiological conditions with a sensitive electrical measurement of binding and activity.

Q. How do you think your research can be carried forward?

Ans. Organelle targeting is an emerging field and needs thorough investigation to study the action of metallodrug inside the biological systems. Introducing selectivity in structural framework of the drugs towards single organelle targeting can make the drug more potent and viable. Other metals are also prominent on anticancer platform, so it is possible to design and synthesize such cost effective and biocompatible metal ligand frameworks which is capable of performing multiple actions with significant potency. The preliminary in vivo results and pharmacokinetics suggested that a detailed study need to perform so that it can be taken to clinical trial.

Q. Give some suggestions to the budding scientists.

Ans. Academia is a never-ending journey full of exciting adventures. It should be spent with utmost pleasure and satisfaction while enjoying science. One should be able to eminence both the personal affairs and professional business. Be clear and rational. Do not hesitate while expressing and talking about yourself, be it stress or mental health imbalance. Also, create another world outside the lab and explore it. Hone your communication skills. In academia, communication is the key to success Always indulge in a teamwork, moreover, in order to be an interdisciplinary scientist, be open to accept and request for collaboration. Do something different which no one thinks is important and invest your efforts and time in it. Learn broadly. Be bold. Be passionate. Establish a name for yourself. Above all, perhaps, to be successful in academia you need to develop your persistence and preserve your creativity no matter what. The key to unlocking the untapped potential is to create and build a path conducive to novelty in science. Make your research plans wisely and execute them in a disciplined way. Always remember, slow and steady wins the race.

source: http://www.indiatomorrow.net / India Tomorrow / Home> Education / by Rashida Bakait, India Tomorrow / May 01st, 2021

Dr. Nahid Kaisar : Towards Next Generation Li-S Battery Technology

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INDIA / Taipei, TAIWAN :

This is the ninth part of the series called ` Scientist Says’ where we bring for our readers the significant research works of young scientists in various fields.

 Dr. Nahid Kaisar is currently working as a postdoctoral fellow in Academia Sinicia, Taiwan. He completed his PhD in Material Science and Engineering from National Taiwan University of Science and Technology, Taiwan. His work is published in several international journals and he has also presented his work in several conferences in USA and Japan. He has also patented his research work for future commercialization.

Here are the excerpts of an interview of Dr. Kaisar with Rashida Bakait of India Tomorrow.

Q. Please briefly explain your research.

Ans: I am working on the development of nanomaterials and their applications on Lithium-ion battery and Lithium-Sulfur battery. I completed my PhD  on the development of Li-S battery, which is also known as next-generation battery technology. We have worked in direct collaboration with industries who manufacture battery for electric car and other applications, which makes the research work more challenging. While working on the materials and its application, always keep in mind about the market viability and industry viability.

At this moment we have well developed Li-ion, Li-polymer battery technology which has wide range of applications that include electric vehicles, consumer electronics and grid technology. But the energy density does not satisfy the current demand. We are doing research on the Li-S battery, which has five times higher energy density and discharge capacity than the current Li-ion battery.

Petrochemical industry produces plenty of Sulfur as by-product, which makes Sulfur abundant element and sulfur is environment friendly compared with the heavy metals used in Li-ion battery. A successfully commercialize Li-S battery not only increase the battery energy density but lower the battery cost.

Q. What was the objective of your research?

Ans: The main objective of my research work on Li-S battery technology is to develop a successful product that is cheaper than recent Li-ion battery and at the same time exhibits higher energy density. The main aim of my research work is to develop a successful Li-S battery that will help to replace the use of toxic heavy metals (like Co, Mn, Ni) which has adverse effects on the environment.

Q. When did you begin and complete your research?

Ans: I started my research in the year 2016 as a graduate student in National Taiwan University of Science and Technology, where I  worked on the thin film technology. Later, in 2017 I started working in Academia Sinica, one of the premier research institutes in Taiwan. I completed my Ph. D in April 2020. Later, in the month of  May 2020 I started working as a postdoctoral fellow in Academia Sinica.

Q. What were the findings of your research?

Ans: There are two aspects of my research work:

  1. Material development: I do research on the design and synthesis of nanomaterials for various applications that include energy storage system. I keep in mind that the synthesis process must be market friendly and easy to process in industry.
  2. Energy storage: Li-S battery face drastic capacity and active materials loss after few charge-discharge cycles. I have successfully developed new materials and battery technology that have successfully stabilized the battery performance.
  3. Q. Any scholarships or awards for research?

Ans: I have been awarded National Taiwan University of Science and Technology graduate scholarship. I have also been awarded CTCI outstanding research award in 2020 for outstanding research work during PhD.

Q. How do you think your research would be beneficial to the industry or society?

Ans: LI-S battery technology is a new topic of research compared to Li-ion battery. My research work adds few innovative research ideas to the field that would help in the development of a commercial product.


Q. Any new research you are working on now.

Ans: Currently, I am working on the development of new anode materials for Li-ion battery. Presently, commercial Li-ion batteries use graphite as anode material, which has lower discharge capacity and low conductivity. I am doing research on new materials that can replace the state-of-the-art graphite while exhibiting similar performance.


Q. How do you think your research can be carried forward?

Ans: Research is a never-ending process. We need to design industry feasible synthesis   process for battery materials using safe and non-toxic materials. We need to collaborate with battery management system that will help to produce an outstanding product. There is a need of strong collaboration between academic and industry to achieve a fruitful product.

Q. Please give few tips and suggestions for the budding scientists.

Ans: All the students who are looking forward to start research journey, should focus on finding an outstanding supervisor. Your supervisor will be the key in success during your research career. University and country play a secondary role.

source: http://www.indiatomorrow.net / India Tomorrow / Home> Education / by Rashida Bakait, India Tomorrow / May 28th, 2021

Dr. Hina Khan: Designing And Synthesizing Organic Molecules

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INDIA / U.S.A :

Dr. Hina Khan

This is the eighth part of the series called `Scientist Says’, where we bring for our readers significant research works of young scientists in various fields.

Dr. Hina Khan started her research journey in year 2014 with Prof. Tushar K. Chakraborty research group, Department of Organic Chemistry, IISc Bangalore. After completing her PhD in July 2019, she worked as a Research Associate in the same lab for a year. In September 2020, she joined a Biocon-group company as a Research Investigator where she worked in collaboration between Bristol Myers Squibb and Syngene International. Currently, she is a postdoctoral fellow at the University of Pittsburgh, United States. She shares her significant research work with Rashida Bakait of India Tomorrow. Here are the excerpts of the interview.

Q. Please briefly explain your research.

Ans. Chemistry is frequently described as the central science and chemical synthesis lies at the heart of the subject. Synthetic organic chemistry underpins several areas of chemistry, including drug discovery, chemical biology, materials science, and engineering. However, the practice of total synthesis of natural products has a rich history of achievements and benefits to science and society that ranges from replicating the molecules of nature in the laboratory to the preparation and production of pharmaceuticals, developing new synthetic strategies and methods, and also synthesizing designed molecules for biology and medicine.

In contributing to the everlasting field of “the art of making molecules”, my research work mainly focuses on the discovery of new organic transformations which are of significant interest to the fields of medicinal chemistry and pharmaceutical development and also uncovering the practical application of Titanocene (III)monochloride in the synthesis of architecturally challenging and biologically important natural products and their inspired synthons.

Q. When did you start and complete your research?

Ans. I started my learning to be a researcher in Aug 2014 with Prof. Tushar K. Chakraborty at IISc, Bangalore, submitted my doctoral thesis in July 2019, and defended the thesis in March 2020. Later in the year 2020, I joined Biocon-group company as a research investigator and worked till April 2021. Currently, I am working as a postdoctoral fellow in University of Pittsburgh, United States.

Q. What was the objective of your research?

Ans. With the ever increasing demand of developing new, efficient, and cheaper methods to construct biologically relevant molecular frameworks, my research aims on the design and developing new synthetic strategies for concise entry to important functionalized bioactive synthetic scaffolds/target.

Q. What were the findings of your research?

Ans. The research findings revolves around two main areas:

I : In developing a synthetic methodology which is flexible and provide single potential route for the diastereoselective construction of diversely substituted 1,3-X,N-heterocyclic variants as valuable scaffolds for natural products and pharmaceuticals, in a diversity-oriented approach. The methodology is amenable for a broad range of substrates based on a metal-free approach.

II. In exploring the synthetic utility of Titanocene(III)monochloride-promoted radical cyclization protocol on to the findings:

a) We have developed a concise and unified approach to gain access to handful iridoid monoterpenes that exhibit wide range of pharmacological activity.

b) We have portrayed a synthetic route to a bicyclic lactone containing a bridgehead hydroxy group, a structure that is present in many natural products of biological and medicinal relevance.

c) Furthermore, an efficient route for the construction of pyrrolo/piperidino[1,2-a]indole derivatives have been developed.

During my research endeavour I have also been involved in the synthesis of sugar amino acid (δ-SAA) based linear lipopeptides (Almiramide analogues) that were screened for their biological activities, viz. antileishmanial and anticancer and the extension of this work is currently active.

Q. What was the conclusion of your research?

Ans. Driven by the ever-increasing demands for small functionalized bioactive scaffolds and the need of broadening the toolbox of unexplored chemical space, our designed strategy provides a flexible route to construct the unique five/six membered 1,3-heterocycles by exploring the synthetic utility of α-phenyl-β-enamino ester following a Mitsunobu-Michael reaction sequence. Next, taking advantage of Cp2Ti(III)Cl-mediated reductive epoxide opening-cyclization, we have developed an expedient and the most concise and unified approach till date in the total synthesis of iridoid monoterpenes in an enantiomerically divergent manner starting from (+)-β-citronellene. Further expansion of the strategy was made to fix hydroxylated bridgehead chiral centre, in the fused/bridged bicyclic lactone, a structure that is present in many natural products of biological and medicinal relevance. Furthermore, as part of our ongoing research interest, we have successfully extended yet another practical application of Ti(III)-mediated epoxide opening-cyclization protocol to devise a simplified route to a pyrrolo/piperido[1,2-a]indole framework, featuring many useful functionalities on the saturated ring, which is ideally suited for further manipulation.

Q. What kind of challenges did you face?

Ans. A doctorate is a long project so your motivation will dip and peak along the way. In multi-step synthesis, designing a synthetic route to the target molecule, optimizing every step of the synthetic plan with the best possible outcome, revising the plan, if needed and starting all-over again is really a burnout process. I would say you can learn more from your failures than successes. They are often catalysts for positive change in the long term. And remember one thing that you are training to be a researcher.

Q. Any scholarships or awards for research?

Ans. For my Ph.D. and Research Associateship (Aug 2014 – Jul 2020), I have received funding from Indian Institute of Science. I have received award for my research work in Indian Peptide symposium, in 2017. Currently, for my postdoctoral program I am receiving scholarship from University of Pittsburgh, United states.

Q. How do you think your research would be beneficial to the industry or society?

Ans. Organic synthesis, the art and science of constructing substances, natural or designed, in the laboratory to replicate the molecules of living creatures, and create other molecules like them, is a remarkable development in human history. Organic synthesis in general, have led to an impressive host of benefits to society, including useful products ranging from pharmaceuticals, dyes, cosmetics and agricultural chemicals to diagnostics and high-technology materials used in computers, mobile phones and spaceships. My research on designing and developing synthetic route to construct heterocycles, terpenoids, alkaloids will provide a new synthetic approach and scope to replicate some of the most intriguing molecules of living nature in the laboratory and apply the developed synthetic strategies to construct variations of them to facilitate biology and medicine.

Q. Any new research you are working on now.

Ans. My current research at University of Pittsburgh, as Post-doctoral fellow is to rationally design and synthesize more efficacious 2-Pralidoxime analogs (2-PAM) which is the only therapeutic countermeasure that is approved by the United States Food and Drug Administration for treating Organophosphorus nerve agents (OPNA) poisoning. However, 2-PAM is not centrally active due to its hydrophilicity and resulting poor blood−brain barrier permeability; hence, these deficiencies warrants the need for antidotes with the development of more hydrophobic analogs.

Q. How do you think your research can be carried forward?

Ans. Taken together, the simplicity and efficiency of the designed strategies can further be adopted to obtain other enticing heterocyclic variants, highly functionalized iridoids/cyclo-pentanoid natural product, also having bridgehead hydroxyl group in a bicyclic lactone, [a]-annulated indole frameworks, which are beneficial to the science of organic synthesis for further innovative applications.

Q. Please give few tips and suggestions to the budding scientists.

Ans. Research is a never-ending journey of learning something new, honing your problem-solving skills and challenging yourself in new ways. I would advise the young scientists to stay curious and stay determined. Science is not easy, become comfortable with failure because a major component of the scientific process is trial and error. Failure is okay! Failing provides some of the biggest learning opportunities and finding new scientific discoveries.

It is not about perfection but curiosity and perseverance. Keep exploring, keep experimenting, keep learning, keep improving. Avoid burnout and look after your mental health to make you more productive in the long run.

Remember to take five-minutes brain break by walking away for a moment, rest that brain and then resume.

source: http://www.indiatomorrow.net / India Tomorrow / Home> Education> Featured / by Rashida Bakait, India Tomorrow / May 19th, 2021