A correlation study of biological activity and molecular docking of Asp and Glu linked bis-hydrazones of quinazolinones.

R. Suhas,H. K. Kumara,M. Shobha,D. M. Suyoga Vardhan,D. Channe Gowda

doi:10.1039/c8ra00531a

Abstract

The present investigation involves the synthesis and spectroscopic and biological activity studies of the bis-hydrazones of quinazolinones derived from aspartic acid and glutamic acid. The antioxidant activities of the compounds were evaluated using DPPH, DMPD and ABTS radical scavenging assays whose results revealed that the IC50 of compounds 6, 7, 11, 12, 20, 21, 25 and 26 was lower than those of the standard references. The anti-inflammatory activity was evaluated with a haemolysis assay using a human blood erythrocytes suspension and the results demonstrated that compounds 8, 9, 13, 14, 22, 23, 27 and 28 were excellent anti-inflammatory agents. In addition, the antibacterial and antifungal activities against various clinical pathogens of human origin revealed that compounds 7, 9, 12, 14, 21, 23, 26 and 28 possessed potent antimicrobial properties. Furthermore, to understand the correlation between biological activity and drug–receptor interaction, molecular docking was performed on the active sites of tyrosine kinase (PDB ID: 2HCK), cyclooxygenase-2 (PDB ID: 1CX2) and glucosamine-6-phosphate (GlcN-6-P) synthase (PDB ID: 2VF5) which showed good binding profiles with the targets that can potentially hold the title compounds. The correlation study revealed that compounds containing EDGs (–OH, –OCH3) were excellent antioxidants, compounds with EWGs (–Cl, –NO2) exhibited good anti-inflammatory activity and compounds bearing –OH and –NO2 groups were very good antimicrobials.

Highlights

Computational biology and bioinformatics play a major role in designing drug molecules and have the potential to speed up the drug discovery process
The synthesis of the desired compounds was achieved according to the steps illustrated in Scheme 1. 3-(4-Oxo-3,4dihydroquinazolin-2-yl)propanoic acid (QZN 1) and 4-(4-oxo3,4-dihydroquinazolin-2-yl)butanoic acid (QZN 2) were synthesized by literature known methods.[26,27,28]
Conjugation of QZN 1/QZN 2 with p-TsOH$NH2–Asp(OBzl)–OBzl/HCl$NH2– Glu(OCH3)–OCH3 was carried out using EDCI/HOBt as the coupling agent and NMM as the base to obtain 1, 2, 15 and 16

Summary

Introduction

Computational biology and bioinformatics play a major role in designing drug molecules and have the potential to speed up the drug discovery process. Molecular docking of the drug molecule with the receptor gives important information about drug–receptor interactions and is commonly used to nd out the binding orientation of drug candidates to their protein targets in order to predict the affinity and activity.[1] Medicinal chemistry is a specialized science that has evolved to encompass a broad range of disciplines concerned with the identi cation, synthesis and development of drug-like compounds for therapeutic use It needs a wide range of expertise, developed through years of training, dedication and learning from best practice in order to produce drugs that are good enough to enter clinical trials with patients.[2].

Chemistry

Biology

Molecular docking studies

Conclusions