Design, Synthesis, and Molecular Docking of 1-(1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine as Potent Nonazole Anticandidal Agent

Abstract

1-(1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine (13) was designed and synthesized as potential nonazole anticandidal agent and precisely characterized by IR,1H NMR,13C NMR, and ESI-MS. The anti-Candidaactivity of13was evaluated against fourCandidaspecies (C. albicans, C. krusei, C. parapsilosis, andC. glabrata). Compound13displayed good anticandidal activities (MIC=0.39, 0.195, 0.39, and 1.56 μmol/mL, resp.) in comparison with that of the standard drug fluconazole (MIC=0.195, inactive, 1.56, and 1.56 μmol/mL, resp.) againstC. albicans, C. krusei, C. parapsilosis, andC. glabrata, respectively. A molecular modeling of the newly synthesized compound13was built in order to investigate its mode of action towards the prospective target cytochrome P450-dependent enzyme lanosterol 14α-demethylase (PDB-code: 1EA1). The docking results showed a similar binding interaction of13and fluconazole at the active site of CYT P450 14α-sterol demethylase. Furthermore, compound13showed no cytotoxicity against normal human breast cell line MCF10A.

A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

“…CYP51 is part of cytochrome P450 superfamily, found both in human and fungal cells. Therefore, it is important to know the possible pharmacokinetic interactions in which the newly synthesized compounds can be involved [29]. All tested compounds act as non-inhibitors of CYP2D6, so drug-drug interactions with compounds that are metabolized by this isoform of CYP450 superfamily are less likely to appear.…”

Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors

“…According to the mechanism of action, there are six classes of antifungal agents: fungal ergosterol synthesis inhibitors (azoles: ketoconazole, fluconazole, and voriconazole), glucan synthesis inhibitors (echinocandins and caspofungin), ergosterol disruptors (polyenes antibiotics: amphotericin B), squalene epoxidase inhibitors (terbinafine and naftifine), chitin synthesis inhibitors (nikkomycin), and nucleic acid synthesis inhibitors (5-fluorocytosine) ( Figure 1) [3]. Due to its high therapeutic index, azoles are first-line drugs for the treatment of invasive fungal infections [4,5].…”

Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

“…In an extension of our ongoing efforts towards developing potent antimicrobial agents [ 35 , 36 , 37 , 38 , 39 ], we synthesized eighteen novel bis-hydrazone derivatives bearing different aryl and heteroaryl rings. The synthetic route was initiated with the preparation of carbohydrazides 3a – c [ 40 ], benzo[ d ]thiazole-2-carbohydrazide 3d [ 35 ] and 3-methylbenzofuran-2-carbohydrazide 3e [ 36 ] ( Scheme 1 ).…”