Jehan Y. Al-Humaidi, Sobhi M. Gomha, AbdElAziz A. Nayl, Ashraf A. Aly, Mahmoud A. A. Ibrahim, Magdi E. A. Zaki, Stefan Braise, Reda A. Haggam
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引用次数: 0
Abstract
Background: Previous studies have reported various biological activities of indeno-pyridazine and thiazole derivatives, including antiviral activity and CoV-19 inhibition. In this pa-per, the authors aimed to design, synthesize, and characterize a novel series of indenopyridazinethi-azoles, starting with 2-(4-cyano-3-oxo-2,3-dihydro-9H-indeno[2,1-c]pyridazin-9-ylidene)-hydra-zine-1-carbothioamide and available laboratory reagents. background: Indenopyridazine and thiazole derivatives have been previously reported to exhibit various biological activities, including antiviral properties. This study builds upon that knowledge to develop new compounds with potential CoV-19 inhibitory effects. Methods: The strategy involved the synthesis of indeno[2,1-c]pyridazincarbothioamide, followed by its reaction with various hydrazonoyl chlorides and α-halocompounds (phenacyl bromides and α-chloroketones) to obtain the desired indenopyridazinethiazole derivatives. The synthesized structures were confirmed using IR, NMR, mass spectra, elemental analysis, and alternative syn-thesis when possible. Docking scores and poses of thirteen synthesized compounds were examined using AutoDock4.2.6 software against multiple targets of SARS-CoV-2, including 3C-like prote-ase (3CLpro), helicase, receptor binding domain (RBD), papain-like protease (PLpro), neuropilin-1 (NRP-1), RNA-dependent RNA polymerase (RdRp), and human angiotensin‐converting enzyme 2 (ACE2). Results: Docking predictions revealed that compound 13d exhibited high potency against 3CLpro and helicase, with docking scores of -10.9 and -10.5 kcal/mol, respectively. Compound 10c showed superior docking scores against RBD and ACE2, with values of -8.7 and -11.8 kcal/mol, respectively. Compounds 10a, 13c, and 7b demonstrated excellent docking scores against RdRp, PLpro, and NRP-1, with values of -10.3, -10.4, and -8.6 kcal/mol, respectively. Conclusion: The authors recommend further experimental assessments of compounds 13d, 10c, 10a, 13c, and 7b against SARS-CoV-2 multi-targets, considering their promising docking scores.
期刊介绍:
Current Organic Synthesis publishes in-depth reviews, original research articles and letter/short communications on all areas of synthetic organic chemistry i.e. asymmetric synthesis, organometallic chemistry, novel synthetic approaches to complex organic molecules, carbohydrates, polymers, protein chemistry, DNA chemistry, supramolecular chemistry, molecular recognition and new synthetic methods in organic chemistry. The frontier reviews provide the current state of knowledge in these fields and are written by experts who are internationally known for their eminent research contributions. The journal is essential reading to all synthetic organic chemists. Current Organic Synthesis should prove to be of great interest to synthetic chemists in academia and industry who wish to keep abreast with recent developments in key fields of organic synthesis.