Design, Synthesis, Antitumor activity, cell cycle analysis and ELISA assay for Cyclin Dependant Kinase-2 of a new (4-aryl-6-flouro-4H-benzo[4, 5] thieno[3, 2-b] pyran) derivatives.

Abstract

<jats:p>A series of benzo[b]thiophene and their benzo[4,5]thieno[3,2-b]pyran derivatives (3a-f), (4a-f), (5a-f) and 6 were synthesized and characterized by spectroscopic and elemental analysis. All compounds were subjected to one dose anticancer screening in NCI- America, but only the compounds gave high percent growth inhibition were further subjected to five dose screening. A good result of compound 4f with GI50 = 0.15 µmol, TGI= 1.14 µmol and 4c with GI50 = 1.09 µmol, TGI = 10.19 µmol, LC50 = 100 µmol on HT-29 cell line. To explore mechanism of cytotoxicity, compound 4f and 4c were allowed to affect cell cycle progression using HT-29 cell line (human colon cancer) in two-time interval (24 and 48 hr). The cytotoxicity of 4f and 4c was correlated with induction of apoptosis causing pre-G1apoptosis and cell growth arrest at G2/M in a time dependant manner through inhibition of CDK-2. For exploring the SAR for all synthesized compounds, IC50 of 5d was determined which was equal to 0.32 ±0.05 µmol, IC50 of 6 was equal to be 0.15 ±0.01 µmol while IC50 of erlotinib reference was equal to 0.3±0.02 µmol. Finally we were able to synthesize a series of benzo[b] thiophene, benzo[4,5]thieno[3,2-b]pyran having a good cytotoxic activity suggesting promising anticancer derivatives.</jats:p>

New benzothieno[2,3-c]pyridines as non-steroidal CYP17 inhibitors: design, synthesis, anticancer screening, apoptosis induction, and in silico ADME profile studies

“…After that, cyclisation of the produced α,β-unsaturated ketones 2a–d with acetamide, 2-chloroacetamide, or 2-cyanoacetamide in the presence of potassium hydroxide as a catalyst afforded the target compounds 3a–d , 4a–d , and 5a–d , respectively, according to a reported procedure 37 . Previous studies in this field showed that compounds containing 3-nitrophenyl moiety at the 4-position of 1,2-dihydro[1]bezothienopyridine ring expressed promising anticancer activity 29 . On this basis, compounds 4d and 5d were chosen in the preparation of other new bezothienopyridine derivatives hoping to obtain compounds potentially active as anticancer agents.…”

Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors

“…The in vitro enzyme inhibition determination for compound 5c was carried out in confirmatory diagnostic unit, Vacsera, Egypt. The evaluation performed profiling of the compound 5c against a range of four protein kinases [VEGFR-2, EGFR, PDGFRβ and CDK-2] by ELISA assay method using staurosporine as a reference according to the previously reported methods [ 40 , 41 , 42 ].…”

Synthesis and Evaluation of Some New 4H-Pyran Derivatives as Antioxidant, Antibacterial and Anti-HCT-116 Cells of CRC, with Molecular Docking, Antiproliferative, Apoptotic and ADME Investigations

“… Examples of pyran-containing compounds with antibacterial [ 33 ], antioxidant [ 34 ] and anticancer activities via inhibition of CDK2 [ 35 , 36 , 37 ]. …”

“…The 4H-Pyran motif is embedded in bioactive 4H-chromene derivatives which display antitumoral and antibacterial effects, such as compounds Ia,b [33], and antioxidant activities, such as derivatives IIa,b [34]. Moreover, compelling evidence has indicated that CDK2 is a valid anticancer target of pyran-containing compounds III-VI, as shown in Figure 2 [35][36][37], due to its pro-tumorigenic role via interference with cell division cycle. [33], antioxidant [34] and anticancer activities via inhibition of CDK2 [35][36][37].…”