Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates

Abstract

Background: Imidazo[2,1-b]thiazole scaffolds were reported to possess various pharmaceutical activities. Results: The novel compound named methyl-2-(1-(3-methyl-6-(p-tolyl)imidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-b]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a–j and 7–9 had produced the respective 1,3,4-thiadiazole derivatives 6a–j and 10–12. The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1H-NMR and 13C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG2). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer. Conclusion: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.

Optical and Thermal Investigations of New Schiff Base/Ester Systems in Pure and Mixed States

“…Schiff base and hydrazone derivatives are well known as valuable intermediates in the synthesis of many organic compounds that are used in a multitude of applications [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. A series of new laterally methoxy Schiff base derivatives A n were prepared according to the following Scheme 2 :…”

New Amino Acid Schiff Bases as Anticancer Agents via Potential Mitochondrial Complex I-Associated Hexokinase Inhibition and Targeting AMP-Protein Kinases/mTOR Signaling Pathway

“…Given the importance of imines (Schiff bases) in the medicinal field and the continuous efforts by our group to develop novel anticancer scaffolds [ 2 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], the aim of this study was first to design and synthesize novel quinazolinone and indole amino acid Schiff bases. The synthesized compounds were then subjected to computer-based docking studies to investigate their binding modes of interaction with the active site of the target enzymes.…”

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

“…The vinyl ketone part of the chalcones is not only responsible for the biological activities of chalcones but is also useful as a key synthon for the preparation of different heterocyclic compounds of pharmacological interest [ 5 ]. Thiazole and chalcone derivatives possess a broad spectrum of bioactivities, including antitubercular [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], anticancer [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], antioxidant [ 33 , 34 , 35 , 36 , 37 , 38 ], antifungal [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] and antibacterial [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The nature of the substituents as...…”