Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents

Jehan Y Al-Humaidi; Sobhi M Gomha; Sayed M Riyadh; Mohamed S Ibrahim; Magdi E A Zaki; Tariq Z Abolibda; Ohoud A Jefri; Amr S Abouzied

doi:10.1021/acsomega.3c05038

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents

ACS Omega. 2023 Sep 5;8(37):34044-34058. doi: 10.1021/acsomega.3c05038. eCollection 2023 Sep 19.

Authors

Jehan Y Al-Humaidi¹, Sobhi M Gomha², Sayed M Riyadh³, Mohamed S Ibrahim², Magdi E A Zaki⁴, Tariq Z Abolibda², Ohoud A Jefri⁵, Amr S Abouzied^{6

7}

Affiliations

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, Saudi Arabia.
³ Department of Chemistry, Faculty of Science, Cairo University, Cairo 12613, Egypt.
⁴ Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
⁵ Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia.
⁷ Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NODCAR), Giza 12311, Egypt.

Abstract

A novel set of thiazolylhydrazonothiazoles bearing an indole moiety were synthesized by subjection reactions of carbothioamide derivative and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity of the synthesized compounds was evaluated against the colon carcinoma cell line (HCT-116), liver carcinoma cell line (HepG2), and breast carcinoma cell line (MDA-MB-231), and demonstrated encouraging activity. Furthermore, when representative products were assessed for toxicity against normal cells, minimal toxic effects were observed, indicating their potential safety for use in pharmacological studies. The mechanism of action of the tested products, as inhibitors of the epidermal growth factor receptor tyrosine kinase domain (EGFR TK) protein, was suggested through docking studies that assessed their binding scores and modes, in comparison to a reference standard (W19), thus endorsing their anticancer activity.