Title:Synthesis, Characterization, and Molecular Modeling Studies of Novel Indenopyridazine-Thiazole Molecular Hybrids
Volume: 22
Issue: 1
Author(s): Jehan Y. Al-Humaidi, Sobhi M. Gomha*, AbdElAziz A. Nayl, Ashraf A. Aly, Mahmoud A. A. Ibrahim, Magdi E. A. Zaki, Stefan Bräse and Reda A. Haggam
Affiliation:
- Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, Saudi Arabia
Keywords:
Thiazole, indenopyridazine, ninhydrin, SARS-CoV-2 multi-targets, docking predictions, oxothiazolidine.
Abstract: Background: Previous studies have reported various biological activities of indeno-pyridazine and thiazole derivatives, including antiviral activity and CoV-19 inhibition. In this paper, the authors aimed to design, synthesize, and characterize a novel series of indenopyridazinethiazoles, starting with 2-(4-cyano-3-oxo-2,3-dihydro-9H-indeno[2,1-c]pyridazin-9-ylidene)-hydrazine-1-car-bothioamide and available laboratory reagents.
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 synthesis when possible. Docking scores and poses of thirteen synthesized compounds were examined using Auto-Dock4.2.6 software against multiple targets of SARS-CoV-2, including 3C-like protease (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 su-perior 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.
