Deepika Maliwal aka Deepika Raghuvir Pissurlenkar

Institute of Chemical Technology Mumbai INDIA

Identification of Novel Potential Anti-Diabetic Candidates targeting Human Pancreatic ?-Amylase and Human ?- Glycosidase: An Exhaustive Structure-based Screening

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Biography

Deepika Maliwal aka Deepika Pissurlenkar is a Research Scholar at the Department of

Pharmaceutical Sciences and Technology at Institute of Chemical Technology, Mumbai,

Maharashtra, India. She has been a faculty with rich experience of teaching and

research in Organic and Medicinal Chemistry. Ms. Deepika is completing her research

in computational chemistry on identification of novel molecules against Lifestyle

Diseases like Diabetes and Dyslipidemia. She has expertise in molecular modeling for

drug design using structure-based and ligand-based methods along with molecular

dynamics simulations of natural and synthetic polymers to understand binding. Ms.

Deepika is graduate and postgraduate from B.R. Nahata College of Pharmacy, Madhya

Pradesh affiliated to Rajiv Gandhi Prodyogik Vishwavidyalaya, Madhya Pradesh where

is also joined later as Assistant Professor. Ms. Deepika has extensive publications in

peer-reviewed journals. She’s currently scouting for post doctoral opportunities in

computational chemistry.

Abstract

c Diabetes is a major health issue that has reached alarming levels with nearly half a billion

people affected worldwide. It is a serious and long-term medical condition with a major

impact on the lives and well-being of individuals, families, and societies at large. Diabetes is

amongst the top 10 diseases responsible for the death amongst adults with an expected rise to

10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. The carbohydrates get

absorbed into the body upon hydrolysis by human pancreatic ?-amylase and other intestinal

enzymes like human ?-glucosidase. The ?-amylase and ?-glucosidase are well validated

therapeutic targets in the treatment of Type II diabetes (T2DM) that play a vital role in

modulating the blood glucose level after a meal. Herein, we report novel and diverse

molecules identified as potential candidates, predicted to have affinity for ?-amylase and ?-

glucosidase. These molecules have been identified via hierarchical multistep docking of

small molecules database with the estimated binding free energies. A Glide XP Score cutoff

?8.00 kcal/mol was implemented to filter out non potential molecules from the database.

Four molecules have been identified after an exhaustive computational study involving the

evaluation of binding interactions and assessment of the pharmacokinetics and toxicity

profiles. The in-depth analysis of protein–ligand interactions was performed using a 100ns

molecular dynamics (MD) simulation to establish the dynamic stability. Furthermore MMGBSA

based binding free energies were computed for 1000 trajectory snapshots to ascertain

the strong binding affinity of these molecules for ?-amylase and ?-glucosidase. The

identified molecules can be considered as promising candidates for further drug development

through necessary experimental assessments.