Synthesis, Characterization, and Molecular Modeling Studies of Novel In-denopyridazine-Thiazole Molecular Hybrids

Title:Synthesis, Characterization, and Molecular Modeling Studies of Novel In-denopyridazine-Thiazole Molecular Hybrids

Volume: 21

Author(s): Jehan Y. Al-Humaidi, Sobhi M. Gomha*, AbdElAziz A. Nayl, Ashraf A. Aly, Mahmoud A. A. Ibrahim, Magdi E. A. Zaki, Stefan Braise and Reda A. Haggam

Affiliation:

• Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, KSA

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 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.

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.

Cite this article as:

Al-Humaidi Y. Jehan, Gomha M. Sobhi*, Nayl A. AbdElAziz, Aly A. Ashraf, Ibrahim A. A. Mahmoud, Zaki E. A. Magdi, Braise Stefan and Haggam A. Reda, Synthesis, Characterization, and Molecular Modeling Studies of Novel In-denopyridazine-Thiazole Molecular Hybrids, Current Organic Synthesis 2024; 21 () . https://dx.doi.org/10.2174/0115701794266795231129074028