Synthesis, Molecular Docking and Preliminary Antileukemic Activity of 4‐Methoxybenzyl Derivatives Bearing Imidazo[2,1‐b][1,3,4]thiadiazole

Abstract

In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1‐b][1,3,4]thiadiazole. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identified two compounds, 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2H‐chromen‐3‐yl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl thiocyanate and 6‐(4‐chlorophenyl)‐2‐(4‐methoxybenzyl)imidazo[2,1‐b][1,3,4]thiadiazole‐5‐carbaldehyde, exhibited the most cytotoxic effect against murine leukemia cells (L1210), human T‐lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC50 values ranging between 0.79 and 1.6 μM. The results indicate that 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2H‐chromen‐3‐yl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl thiocyanate is inducing phosphatidylserine externalization and caspase‐3 activation which are both a hallmark of apoptosis. Docking studies showed that 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2H‐chromen‐3‐yl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl thiocyanate binds within the active sites of transforming growth factor beta (TGF‐β) type I receptor kinase domain by strong hydrogen binding and hydrophobic interactions.

Novel Furan‐Pyrazole Molecular Hybrids as Prospective Anti‐Neuroinflammatory Agents: Design, Synthesis, and In‐Vitro Screening Thereof

“…The XP Glide score was calculated based on the binding interaction, Van der Waals, electrostatic potential, and strain energy calculation. The binding of the ligands with HMGB1 (PDB ID: 2LY4) and HMGB1 Box A (PDB ID: 4QR9) was examined using the Schrödinger Maestro interface (Schrödinger 11.8) [21] …”

“…The binding of the ligands with HMGB1 (PDB ID: 2LY4) and HMGB1 Box A (PDB ID: 4QR9) was examined using the Schrödinger Maestro interface (Schrödinger 11.8). [21]…”

Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo[2,1-b][1,3,4]thiadiazoles

“…The imidazo ring [2,1-b] was fused with 2-amino-1,3,4-thiadiazole, which resulted in imidazo [2,1-b] [1,3,4]thiadiazole with antibacterial [4][5][6], antifungal [7], anti-inflammatory [8,9], anticancer [10], analgesic [11], and antitubercular properties [12,13]. We have reported imidazo [2,1-b] [1,3,4]thiadiazoles (II) as cytotoxic agent [14][15][16][17][18][19]. Recent studies have reported experiments on imidazo [2,1-b] [1,3,4] thiadiazoles (III) as non-steroidal ecdysone agonists [20].…”