Synthesis and In Silico Study of Some New bis-[1,3,4]thiadiazolimines and bis-Thiazolimines as Potential Inhibitors for SARS-CoV-2 Main Protease

Sobhi M Gomha; Sayed M Riyadh; Magda H Abdellattif; Tariq Z Abolibda; Hassan M Abdel-Aziz; AbdElAziz A Nayl; Alaa M Elgohary; Abdo A Elfiky

doi:10.3390/cimb44100311

Synthesis and In Silico Study of Some New bis-[1,3,4]thiadiazolimines and bis-Thiazolimines as Potential Inhibitors for SARS-CoV-2 Main Protease

Curr Issues Mol Biol. 2022 Sep 30;44(10):4540-4556. doi: 10.3390/cimb44100311.

Authors

Sobhi M Gomha¹, Sayed M Riyadh^{2

3}, Magda H Abdellattif⁴, Tariq Z Abolibda¹, Hassan M Abdel-Aziz⁵, AbdElAziz A Nayl⁶, Alaa M Elgohary⁷, Abdo A Elfiky⁷

Affiliations

¹ Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
³ Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia.
⁴ Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Department of Chemistry, Faculty of Science, Bani Suef University, Bani Suef 62521, Egypt.
⁶ Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Saudi Arabia.
⁷ Department of Biophysics, Faculty of Science, Cairo University, Giza 12613, Egypt.

Abstract

A novel series of bis-[1,3,4]thiadiazolimines, and bis-thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1'-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α-haloketones, respectively. Docking studies were applied to test the binding affinity of the synthesized products against the M^pro of SARS-CoV-2. The best compound, 5h, has average binding energy (-7.50 ± 0.58 kcal/mol) better than that of the positive controls O6K and N3 (-7.36 ± 0.34 and -6.36 ± 0.31 kcal/mol). Additionally, the docking poses (H-bonds and hydrophobic contacts) of the tested compounds against the M^pro using the PLIP web server were analyzed.

Keywords: SARS-CoV-2 Mpro; bis-(3-phenylthiourea); hydrazonoyl halides; molecular docking; α-haloketones.

Grants and funding

This research received no external funding.