Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants

Abstract

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 μg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.

Design, Synthesis, Molecular Docking, and Evaluation Antioxidant and Antimicrobial Activities for Novel 3-Phenylimidazolidin-4-One and 2-Aminothiazol-4-One Derivatives

“…Previously, we have designed and synthesized a novel series of 1 H -3-indolyl derivatives, which achieved high levels of activities as antioxidants [ 22 ]. Our vision in this work is to synthesize two novel series of promised five-membered rings: imidazoles and thiazoles.…”

“…In our previous work, we designed and synthesized some new antioxidant compounds [ 22 ]. Continuing our efforts in this approach, we designed and synthesized a new series of promising antioxidant candidates.…”

“…In addition, imidazopyrimidines exhibited highly biological activities where they act as anti-inflammatory [ 19 ], antimicrobial [ 20 ], and cytotoxic agents [ 21 ]. Researchers designed effective drugs by reacting pyridine ring with nucleus pyrimidine ring as antioxidants [ 22 ], antimicrobial [ 23 ], and anticancer [ 24 ]. So, Hugh efforts have been made to construct this category of these heterocyclic candidates by inspired scientists [ 22 , 23 , 24 ].…”

“…Researchers designed effective drugs by reacting pyridine ring with nucleus pyrimidine ring as antioxidants [ 22 ], antimicrobial [ 23 ], and anticancer [ 24 ]. So, Hugh efforts have been made to construct this category of these heterocyclic candidates by inspired scientists [ 22 , 23 , 24 ]. Moreover, in light of the relevance of the aforementioned concerns and our ongoing efforts to synthesize novel condensed imidazole and thiazole systems, we present in this paper utilization imidazoldin-4-one, and thiazol-4-one as reactive synthones for the development of some novel fused thiols, imidazoles, purines, and pyrimidines, respectively.…”

Newly synthesized series of oxoindole–oxadiazole conjugates as potential anti-SARS-CoV-2 agents:in silicoandin vitrostudies

“…One of the most important and recent approaches to investigate the activity of a drug is computer-aided drug design (CADD). [39][40][41][42][43][44][45][46][47][48][49] In this study, the interaction between the designed compounds and the binding site was predicted using molecular docking to calculate the binding affinities. 50 Moreover, to confirm the results of molecular docking, molecular dynamics (MD) simulations for 100 ns were carried out on the best-docked inhibitor-protein complexes.…”