78364-55-3Relevant articles and documents
Synthesis, in vitro antitumor activity and molecular modeling studies of a new series of benzothiazole Schiff bases
Gabr, Moustafa T.,El-Gohary, Nadia S.,El-Bendary, Eman R.,El-Kerdawy, Mohamed M.,Ni, Nanting
, p. 380 - 386 (2016)
A new series of benzothiazole Schiff bases 3-29 was synthesized and screened for antitumor activity against cervical cancer (Hela) and kidney fibroblast cancer (COS-7) cell lines. Results indicated that compounds 3, 14, 19, 27 and 28 have promising activity against Hela cell line with IC50 values of 2.41, 3.06, 6.46, 2.22 and 6.25 μmol/L, respectively, in comparison to doxorubicin as a reference antitumor agent (IC50 2.05 μmol/L). In addition, compound 3 displayed excellent activity against COS-7 cell line with IC50 value of 4.31 μmol/L in comparison to doxorubicin (IC50 3.04 μmol/L). In the present work, structure based pharmacophore mapping, molecular docking, protein-ligand interaction, fingerprints and binding energy calculations were employed in a virtual screening strategy to identify the interaction between the compounds and the active site of the putative target, EGFR tyrosine kinase. Molecular properties, toxicity, drug-likeness, and drug score profiles of compounds 3, 14, 19, 27, 28 and 29 were also assessed.
Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
Chen, Ge,Niu, Chunyi,Yi, Jianhua,Sun, Lin,Cao, Hengyi,Fang, Yanjia,Jin, Taijie,Li, Ying,Lou, Chunli,Kang, Jingwu,Wei, Wanguo,Zhu, Jidong
, p. 3107 - 3121 (2019/04/01)
Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC25 (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10-Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.
Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists
Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Javed, Kalim,Bano, Sameena,Ali, Yakub,Dhulap, Abhijeet,Alam, Perwez,Pasha, M. A. Qadar
, p. 354 - 362 (2016/10/19)
Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.
