Research
Combating Alzheimer's disease with chemical probes
Alzheimer’s disease (AD), a complex neurodegenerative disorder is mainly affecting the aged populations. Progression of the disease leads to the loss of memory and other cognitive impairments. AD has proven to be extremely difficult choice for drug developers due to its multi-faceted nature. The smaller number of drugs for the treatment of AD and high failure rates of drug candidates in clinical trials demands potential therapeutic probes.
Making use of sophisticated computational tools, in vitro assays and biophysical characterizations I am trying to suggest efficient chemical probes for major drug targets (acetylcholinesterase, NMDAR, BACE and glutaminyl cyclase) in AD.
Novel anti-inflammatory agents from natural and synthetic sources
Recurrent inflammation that occurs as a part of the complex biological system is always dangerous and often found to associated with various life-threatening diseases like rheumatoid arthritis, asthma, cancer, neurodegenerative diseases, etc.
Classical enzymes such as Phospholipase A2, Lipoxygenase and Cyclooxygenase-2 that are involved in the arachidonic acid pathways were used for the inhibitor discovery. In our studies, various natural and synthetic molecules were investigated against these enzymes and their inhibitory profiles were explored. Natural products such as curcumin, curcumin analogues, piperine, piperine analogues, different fatty acids, anti-oxidants like NDGA, morin are some of the promising natural molecules etc were already reported against these enzymes.
Development of small molecules/peptides to inhibit protein aggregation
The process of accumulation of protein aggregates, ‘amyloidosis’ can be formed from different protein. Amyloidosis associated with disease like Parkinson’s diseases, Alzheimer’s diseases (AD), Amyotrophic lateral sclerosis and Autosomal hereditary systemic amyloidosis etc. Protein deposits impair the normal functioning of the organs and can also leads to life-threatening organ failure.
In ‘autosomal hereditary systemic amyloidosis’, lysozyme and its variants undergo amyloidosis. Structure based designing of chemical agents that can be stop the lysozyme aggregation might be potential therapeutic agents. Hence, I am trying to provide functional and mechanistic understanding to the lysozyme aggregations and its link towards the disease.
Unlocking the receptor-drug interactions through bio-macromolecular crystallography
Biological macromolecules plays key roles in almost every biological process. The 3D structures of biological macromolecules determined by X-ray crystallography, are considered as the ‘gold standard’ of data describing the molecular architecture of important proteins and nucleic acids. Hence, macromolecular X-ray crystallography has become an indispensable and powerful technique to the drug discovery process where the 3D structure of a drug target is acting as a key component in the entire process. Detailed analysis of protein-ligand complexes allows to study specific interactions of a drug molecules with its protein target. Hence, to provide a platform for the structure based drug discovery, I am trying to perform macromolecular crystallogrpahy for different biomacromolecules.
Tackling bacterial and fungal enzymes for the designing of antimicrobial anti-fungal agents
Many fungi produce alpha amylase to convert starch into simple sugars that is used as the energy source for the organisms.
We found out alpha amylase inhibitors can inhibit the growth of fungi by restricting the availability of their food. Inhibiting the growth of Aspergillus flavus by targeting alpha amylase with phytochemicals is being attempted in this research with a focus of designing promising anti fungal agents.
Antibiotic resistance has become an alarming problem for clinicians worldwide. Beta-lactamase inhibitors can be combined with a susceptible antibiotics to restore its activity against beta-lactamase-producing organisms. This has been proven to be an effective strategy for overcoming antibiotic resistance. Hence studies are performing to find out potential beta lactamase inhibitors.