3174-15-0Relevant articles and documents
Design, synthesis, molecular docking and antiproliferative activity of some novel benzothiazole derivatives targeting EGFR/HER2 and TS
Abdellatif, Khaled R. A.,Amin, Noha H.,Belal, Amany,El-Saadi, Mohamed T.,Hemeda, Loah R.,Said, Eman G.
, (2020)
Multi-targeted anticancer drugs are in focus as a promising research topic. A new series of benzothiazoles hybridized with pyrimidine moiety was designed and synthesized using the lead compound 4a. Various chemical modifications on the pyrimidine ring of 4a at four different positions were done in a trial to get new multi-targeted anticancer agents. The structures of the newly synthesized compounds were established on their elemental analyses and spectral data. All final synthesized derivatives were submitted to the National Cancer Institute (NCI), USA, to be screened for their in vitro anticancer activity. Further evaluation for the cytotoxic activity of the most active compounds was performed using the MTT assay method. Compounds 4d, 8d, 8h, 8i and 17 were then selected for examining their in vitro enzyme inhibitory activities against EGFR, HER2 and TS enzymes using lapatinib and 5FU as standards. Furthermore, cell cycle analysis and apoptosis induction detection were also evaluated. Finally, molecular docking studies were carried out for compounds 4d, 8d, 8h, 8i and 17 to interpret their observed enzymatic activities based on the ligand–protein interactions.
Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety
Havrylyuk, Dmytro,Mosula, Ludmyla,Zimenkovsky, Borys,Vasylenko, Olexandr,Gzella, Andrzej,Lesyk, Roman
, p. 5012 - 5021 (2010)
Antitumor screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. Reactions of (benzothiazole-2-yl)hydrazine with trithiocarbonyl diglycolic acid or 6-methyl-2-aminobenzothiazole with 2-carbethoxymethylthio-2-thiazoline-4-one have yielded starting 3- (1) or 2-substituted (11) 4-thiazolidinones which have been subsequently utilized in a Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 2-10, 12-16. Compound 11 has been obtained alternatively by a counter synthesis method based on the reaction of 2-chloro-N-(6-methylbenzothiazol-2-yl)-acetamide and ammonium thiocyanate. The structures of compounds have been determined by 1H, 13C NMR, IR and X-ray analysis. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute and two (6, 16) of them has revealed the anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancers cell lines. Among tested compounds, 2-{2-[3-(benzothiazol-2-ylamino)-4- oxo-2-thioxothiazolidin-5-ylidenemethyl]-4-chlorophenoxy}-N-(4-methoxyphenyl) -acetamide (6) was found to be the most active candidate with average logGI 50 and logTGI values -5.38 and -4.45 respectively.
Mechanistic insights into binding of ligands with thiazolidinedione warhead to human histone deacetylase 4
Basheer, Sidra,J?nsch, Niklas,Müller, Marlene,Meyer-Almes, Franz-Josef,Ramaa, C. S.,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha,Wozny, Ewelina,Wurster, Eva
, (2021/10/26)
Recently, we have reported that non-hydroxamate thiazolidinedione (TZD) analogs are capable of inhibiting human deacetylase 4 (HDAC4). This study aims at the dissection of the molecular determinants and kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants. The experimental data were rationalized by docking to the two major conformations of HDAC4. TZD ligands are competitive inhibitors and bind via a two-step mechanism involving principal molecular recognition and induced fit. The residence time of 24 g is (34 ± 3) min and thus much larger than that of the canonical pan-HDAC inhibitor SAHA ((5 ± 2) min). Importantly, the binding kinetics can be tuned by varying the structure of the CAP group.
Biological evaluation of a series of benzothiazole derivatives as mosquitocidal agents
Sever, Belgin,Altlntop, Mehlika Dilek,?zdemir, Ahmet,Tabanca, Nurhayat,Estep, Alden S.,Becnel, James J.,Bloomquist, Jeffrey R.
, p. 288 - 294 (2019/07/04)
Aedes aegypti is associated with the transmission of numerous human and animal diseases, such as yellow fever, dengue fever, chikungunya, and more recently Zika virus. Emerging insecticide resistance has created a need to develop new mosquitocidal agents for effective control operations. A series of benzothiazole-piperidine derivatives (1-24) were investigated for their larvicidal and adulticidal effects on Ae. aegypti It was observed that compounds 2, 4, 6, 7, 8, 11 and 13 showed notable larvicidal activity. Furthermore, compounds 6 and 10 showed promising adulticidal activity. Based on the mosquitocidal properties of these compounds, docking studies were also carried out in the active site of the AeSCP2 enzyme to explore any insights into further in vitro enzyme studies. Docking results indicated that all these active compounds showed reasonable interactions with critical residues in the active site of this enzyme. This outcome suggested that these compounds might show their larvicidal and adulticidal effects via the inhibition of AeSCP2. According to in vitro and in silico studies, compounds 2, 4, 6, 7, 8, 10, 11 and 13 stand out as candidates for further studies.
