Synthesis, Characterization, and Molecular Modeling Studies of Novel In-denopyridazine-Thiazole Molecular Hybrids-Reference-Cited by-同舟云学术

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

Published:2024-02-12 Issue: Volume:21 Page:
ISSN:1570-1794
Container-title:Current Organic Synthesis
language:en
Short-container-title:COS

Author:

Al-Humaidi Jehan Y.¹,Gomha Sobhi M.²,Nayl AbdElAziz A.³,Aly Ashraf A.⁴,Ibrahim Mahmoud A. A.⁵⁶,Zaki Magdi E. A.⁷,Braise Stefan⁸⁹,Haggam Reda A.²¹⁰

Affiliation:

1. Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O .BOX, 84428, Riyadh, 11671, Saudi Arabia

2. Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah, 42351, KSA

3. Department of Chemistry, College of Science, Jouf University, Sakaka, 72341, Al Jouf, Saudi Arabia

4. Chemistry Department, Faculty of Science, Organic Division, Minia University, El-Minia, 61519, Menia, Egypt

5. Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt

6. School of Health Sciences, University of Kwa-Zulu-Natal, Westville, Durban, 4000, South Africa

7. Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia

8. Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76133, Karlsruhe, Germany

9. Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Director Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

10. Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44511, Egypt

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.

Publisher

Bentham Science Publishers Ltd.