Synthesis, Characterization, Bioactivity Screening and Computational Studies of Diphenyl−malonohydrazides and Pyridines Derivatives

Abstract

A series of new hydrazide (3 a-j) and pyridine (11 a-j) derivatives were synthesized using a convergent synthetic methodology by condensation of malono-di(2-phenylhydrazide) with arylidene malononitrile or arylidene ethyl cyanoacetate derivatives. The synthesized compounds (3, 11 a-j) were characterized using via IR, 1 H-, 13 C-NMR, and MS spectroscopies as well as elemental analysis. The biological activity of these molecules has been evaluated in vitro against two grampositive bacteria (Staphylococcus aureus and Streptococcus pneumoniae) and one-gram negative bacteria (Escherichia coli), as well as one fungus (Candida albicans). The results of the bioactive assay revealed that the synthesized pyridine (11 a-j) derivatives had greater antibacterial efficacy than the hydrazide (3 a-j) derivatives and were comparable to the reference drug Augmentin. Furthermore, docking studies against the Staphylococcus aureus dihydrofolate reductase (DHFR) protein revealed that pyridine derivatives (11 a-j) had higher binding interactions affinity (ΔG = À 9.59 ∼ À 7.69 kcal/mol) than diphenylÀ malonohydrazide derivatives (3 a-j), which achieved a binding affinity in the range of (ΔG = À 9.65 ∼ À 6.77 kcal/ mol), supporting the experimental results. Finally, DFT and TD-DFT were used to gain a better understanding of the structureactivity relationship and biological activity of the new synthesized hydrazide/pyridine derivatives.

Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays

“…The docking analysis was performed to explicate the potency of these desirable molecules in vitro against the EGFR, MMP-2, and hCAII proteins, respectively, through their potential interaction mechanisms with their crystal frameworks (PDB: 4HJO [77], 1HOV [78], 3M04 [79]). The docking investigation procedures were implemented using Glide's module ® [80][81][82][83][84]. The preliminary inhibitors (Erlotinib, hydroxamic acid, and sulfonamide) were redocked into the examined crystal frameworks to verify the docking methodology.…”