40106-15-8Relevant academic research and scientific papers
Synthesis, anticancer activity and effects on cell cycle profile and apoptosis of novel thieno[2,3-d]pyrimidine and thieno[3,2-e] triazolo[4,3-c]pyrimidine derivatives
Kandeel, Manal M.,Refaat, Hanan M.,Kassab, Asmaa E.,Shahin, Inas G.,Abdelghany, Tamer M.
, p. 620 - 632 (2014)
Motivated by the widely reported anticancer activity of thieno[2,3-d]pyrimidines a series of 24 new 2-substitutedhexahydrocycloocta[4,5] thieno[2,3-d]pyrimidines with different substituents at C-4 position and hexahydrocycloocta[4,5]thieno[3,2-e]-1,2,4-triazolo[4,3-c]pyrimidines were synthesized. The anticancer activity of 17 compounds were evaluated by National Cancer Institute (USA) using a two stage process utilizing 59 different human tumor cell lines representing leukemia, melanoma, cancers of lung, colon, central nervous system (CNS), ovary, kidney, prostate as well as breast. Compound 9c showed broad spectrum potent anticancer activity in nano molar to micro molar range against 56 human tumor cell lines with GI50 less than 10 μM ranging from 0.495 to 5.57 mM, also it is worth mentioning that compound 9c had the marked highest selectivity against the two cell lines T-47D and MDA-MB-468 belonging to breast cancer with GI50 = 0.495 and 0.568 mM respectively, and its effect was further studied on cell cycle progression and induction of apoptosis in the MDA-MB-468 cell line. Results showed that compound 9c induced cell cycle arrest at G2/M phase and also, showed accumulation of cells in pre-G1 phase which may result from, degradation or fragmentation of the genetic materials indicating a possible role of apoptosis in compound 9c-induced cancer cell death and cytotoxicity and verifying this compound as promising selective anticancer lead. Compound 6c was selective against K-562, SR and MOLT-4 cell lines belonging to leukemia showing growth inhibition percentages 86.38, 65.76 and 60.40 at a single dose test, at the same time it showed lethal activity against HOP-92 representing non-small cell lung cancer. Interestingly, leukemia SR, CNS cancer SNB-75 and renal cancer UO-31 cell lines proved to be sensitive to compound 6d with growth inhibition percentages 52.86, 50.94 and 53.99 respectively. Additionally, compound 6d demonstrated lethal activity to HOP-92 belonging non-small cell lung cancer.
Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3- carboxamides and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from known antimycobacterial lead
Nallangi, Radhika,Samala, Ganesh,Sridevi, Jonnalagadda Padma,Yogeeswari, Perumal,Sriram, Dharmarajan
, p. 110 - 117 (2014/03/21)
Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c] pyridine-3-carboxamide and ten of 2-substituted 4,5,6,7,8,9- hexahydrocycloocta[b]thiophene-3-carboxamide were synthesized by molecular modification of a known antimycobacterial molecule. Compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9- hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most active compound against MTB with MIC of 3.70 μM and was more potent than Ethambutol (MIC of 7.64 μM), Ciprofloxacin (MIC of 9.41 μM) and standard lead compound SID 92097880 (MIC of 9.15 μM). Compound 12f also showed MTB MIC of 1.23 μM in the presence of an efflux pump inhibitor verapamil, and showed no cytotoxicity at 50 μM.
Synthesis and anticancer activity of novel 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine derivatives
Kassab, Asmaa E.,Gedawy, Ehab M.
, p. 224 - 230 (2013/07/27)
A series of new 2-pyridyl hexahydrocycloocta [4,5]thieno[2,3-d]pyrimidines with different substituents as C-4 position was synthesized. The anticancer activity of the newly synthesized compounds was tested in vitro using a two-stage process utilizing 60 different human tumor cell lines representing leukemia, melanoma and cancers of lung, colon, central nervous system, ovary, kidney, prostate as well as breast. Compounds 4a, 6a, 7a, 7d and 7g showed potent anticancer activity at low concentrations against most of the used human tumor cell lines comparable with doxorubicin as standard potent anticancer drug (average log10 GI50 over all cell lines = -6.85). Also, compound 4b was selective against SNB-75 (CNS cancer) log10 GI 50 = -5.57. Interestingly, compound 7e exhibited promising selectivity against 13 tumor cell lines showing growth inhibition percentages between 54.05 and 89.23.
Exploiting drug-resistant enzymes as tools to identify thienopyrimidinone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H
Masaoka, Takashi,Chung, Suhman,Caboni, Pierluigi,Rausch, Jason W.,Wilson, Jennifer A.,Taskent-Sezgin, Humeyra,Beutler, John A.,Tocco, Graziella,Le Grice, Stuart F. J.
supporting information, p. 5436 - 5445 (2013/07/26)
The thienopyrimidinone 5,6-dimethyl-2-(4-nitrophenyl)thieno[2,3-d] pyrimidin-4(3H)-one (DNTP) occupies the interface between the p66 ribonuclease H (RNase H) domain and p51 thumb of human immunodeficiency virus reverse transcriptase (HIV RT), thereby indu
Synthesis of potent anticancer thieno[2,3-d]pyrimidine derivatives
Kandeel,Mounir, Ashraf A.,Refaat, Hanan M.,Kassab, Asmaa E.
scheme or table, p. 266 - 275 (2012/09/22)
As part of our program to identify novel cytotoxic agents, various series of hexahydrocycloocta[4,5]thieno[2,3-d] pyrimidines and pyrimidin-4-ones substituted by aryl at the C-2 position together with phenylethylamino, substituted amino, hydrazinyl or arylidenhydrazinyl substituents at the C-4 position were synthesised. These compounds were prepared as bioisosteres of gefitinib, an antitumour drug used for the treatment of gastrointestinal stromal tumours. All compounds exhibited antitumour activity against (HCT 116) cell line in vitro. Eight compounds (IC50: 3.89, 4.65, 6.63, 6.94, 7.89, 9.53, 12.00 and 12.30 μg mL-1, respectively) exhibited 4.3 to 1.3 fold more potent antitumour activity than imatinib (IC50: 16.93 μg mL-1). Also, a docking study of the newly synthesised compounds with the active site of CDK2 was described.
The synthesis and biological evaluation of 2-amino-4,5,6,7,8,9- hexahydrocycloocta[b]thiophenes as allosteric modulators of the A1 adenosine receptor
Aurelio, Luigi,Christopoulos, Arthur,Flynn, Bernard L.,Scammells, Peter J.,Sexton, Patrick M.,Valant, Celine
supporting information; experimental part, p. 3704 - 3707 (2011/08/06)
A series of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes were prepared and evaluated as potential allosteric modulators of the A1 adenosine receptor (AR). The structure-activity relationships of the 3-position were explored along with va
