New Approaches and Advancements in Drug Development from Phenolic P-coumaric Acid.

P-coumaric acid is a common dietary polyphenol present in fruits, vegetables, and cereals in conjugated and free form. The toxicity profile of the drug is very low, and it exhibits many pharmacological actions (antihypertensive, anti-inflammatory, anticancer, antimicrobial activity, antidiabetic, anticancer, and antioxidant effect). P-coumaric acid also acts as a free radical scavenger and inhibits various enzymes, which generate free radicals. It is also used as the raw material for the preparation of preservatives, vanillin, sports foods, skin defense agents, and as a cross-linker for the formation of edible films and food gels. The current study is based upon biological effectiveness, molecular docking, SAR, sources of p-coumaric acid, and related derivatives.

In silico design and synthesis of targeted rutin derivatives as xanthine oxidase inhibitors.

BACKGROUND: Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research rutin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. OBJECTIVE: To develop new xanthine oxidase inhibitors from natural constituents along with antioxidant potential. METHOD: In this report, we designed and synthesized rutin derivatives hybridized with hydrazines to form hydrazides and natural acids to form ester linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. RESULTS: The enzyme kinetic studies performed on rutin derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC50 value ranging from 04.708 to 19.377 µM and RU3a 3 was revealed as most active derivative. Molecular simulation revealed that new rutin derivatives interacted with the amino acid residues PHE798, GLN1194, ARG912, GLN 767, ALA1078 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential. CONCLUSION: Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity.

Mechanistic approach towards interaction of newly synthesized Hesperidin derivatives against xanthine oxidase.

Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research Hesperidin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. The design and synthesis of Hesperidin derivatives hybridized with hydrazines to form hydrazides and anilines was performed with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. The enzyme kinetic studies performed on newly synthesized derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC50 value ranging from 00.263 µM - 14.870 µM and 3HDa1 was revealed as most active derivative. Molecular simulation revealed that new Hesperidin derivatives interacted with the amino acid residues PHE798, GLN1194, ARG912, THR585, SER1080 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential. Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity.