In silico Exploration of Phytochemical based Thiazolidinone- Caffeic Acid- Indole New Chemical Entities for Simultaneous Management of Diabetes and Hypertension- A Fascinating Study.

Background: Past few decades have witnessed the co-existence of diabetes and hypertension leading to other health disorders. Hence, it is imperative to look into new therapies for the treatment of both hypertension and diabetes simultaneously in order to gradually reduce the pill burden and subsequent side effects.

Objective: The goal of the current work was to use several in silico methods to develop new entities that have both anti-diabetic and anti-hypertensive activity.

Methods: Structure activity relationship was drawn from the literature considering Thiazolidinones (Anti diabetes), Indole (Antihypertensive) and naturally occurring polyphenols (Dual activity) for simultaneous management of hypertension and diabetes. Fifty-six new chemical entities were designed and subjected to ADME and docking studies. Based on the Lipinski filter, bioavailability and lead likeness nineteen molecules were further docked into three PDB's (5Y2T, 4BVN, 1O8A).

Results: The majority of the NCE's have shown higher binding affinities than the standard drugs, with Compound 42 having the best results. Among nineteen NCE's, 50% of the compounds have shown the involvement of Thiazolidinone, Indole and Catechol pharmacophores with prominent hydrogen bonds, hydrophobic, electrostatic and pi-pi stacking interactions with all three PDB's signifying their potential dual activity. Most favourable interactions were shown by compound 42.

Conclusion: The results obtained are encouraging for further exploration of the hit molecules for simultaneous treatment of the two diseases.