Antiproliferative activity of novel thiophene and thienopyrimidine derivatives.

A novel series of newly synthesized thiophene derivatives, ethyl-4,5-dimethyl-2-(3-(3,4,5-trimethoxyphenyl)thioureido)thiophene-3-carboxylate 3, ethyl-2-[(2-(dimethylamino)ethoxy)mercapto)methyleneamino)]-4,5-dimethyl-thiophene-3-carboxylate 9, thienopyrimidines 4, 7, 10-20, triazolothienopyrimidines 5, 6 were prepared and tested for their antiproliferative activity. The structures of the synthesized compounds were confirmed on the basis of elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data. The results showed that the synthesized compounds were more active on breast cancer than on colon cancer cell lines and the most potent compounds in this study are compounds 3 and 13 which exerted remarkable activity against MDA-MB-231 (breast cancer) and HT-29 (colon cancer) cell lines with IC50 values (40.68, 49.22 µM) for compound 3 and (34.04, 45.62 µM) for compound 13. Also, compounds 4-6, 9 showed a moderate activity against breast cancer cell line, while compounds 15, 19 and 20 showed no activity.

Anticancer activity of novel thiophenes containing a biological active diphenylsulfone, diazepin, piperidine, oxazepine, acryladehyde and sulfonamide moieties.

A variety of thiophene derivatives bearing diphenylsulfone 3,4, diazepines 5b, 6b, phenylamino 7, piperidine 8, benzylpiperidine 9, oxazepines 10b, 11b, acrylaldehydes 12-14 and benzeonesulfanamide 15 were synthesized. some newly synthesized compounds were evaluated for their in vitro cytotoxic activity against human tumor breast cancer cell lines. The tested compounds showed moderate to good cytotoxic activity and indeed, some of them were more potent than doxorubicin as a reference drug.

Novel pyrazole derivatives as anticancer and radiosensitizing agents.

The present article describes the synthesis of some novel pyrrole, pyrazolo[4,3-d]oxazole, pyrrolo[2,3-b]pyridine, 1,2,3-triazole and oxoazetidin derivatives incorporating pyrazole moiety, the structures of which were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in-vitro antitumor activity against liver and colon human tumor cell lines (HEPG2 and HCT), furthermore, the most potent compounds were evaluated for their ability to enhance the cell killing effect of γ-radiation (radiosensitizing evaluation). The results of in-vitro anticancer evaluation showed that compounds 3 and 16a were the most potent compounds on HEPG2 (IC50=2.6 and 4.2 µg/ml) and compounds 2 and 10 were the most potent on HCT (IC50=2.7 and 3.9 µg/ml) compared to vinblastine (IC50=4.6 on HEPG2 and 2.6 µg/ml on HCT), while, the activity of the most potent compounds increased after combination with γ-radiation and they showed no toxicity on normal hepatocytes and colon cells at their effective concentrations.

Synthesis, in-vitro anticancer screening and radiosensitizing evaluation of some new N-(quinoxalin-2-yl)benzenesulfonamide derivatives.

The objective of this work is to synthesize and investigate the anticancer activity of a new series of sulfaquinoxaline derivatives by incorporating biologically active moieties (thiourethane, thiazole, imidazole, imidazopyrimidine, imidazopyrimido-pyrimidine, thienopyrimidine, benzopyrimidinone, benzothiazole, thiazole and pyridine moieties). All the newly synthesized compounds were evaluated for their in-vitro anticancer activity against human liver cell line (HEPG2). All the tested compounds showed comparable activity to that of the reference drug 5-fluorouracil (IC50=40 µM), and the most potent compounds were found to be compounds 4 and 17 (IC50=4.29 and 11.27 µM, respectively). On the other hand, the most potent compounds 4 and 17 were evaluated as radiosensitizing agents.

Synthesis, anticancer activity and radiosensitizing evaluation of some new 2-pyridone derivatives.

Based on the reported anticancer activity of 2-pyridone, a new series of 6-amino-5-cyano-1-(3-ethylphenyl)-2-oxo-4-substituted-1,2-dihydropyridine-3-carbo-nitriles 4a-p were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line and liver human tumor cell line (HEPG2). Radiosensitizing activity was also evaluated. The starting material 2-cyano-N-(3-ethylphenyl)-acetamide 3 was obtained via reaction of 3-ethyl aniline 1 with ethyl cyanoacetate under condition of fusion. Upon treatment of compound 3 with aromatic aldehyde and malononitrile in the presence of catalytic amount of piperidine yielded the corresponding 1,2-dihydropyridine derivative 4a-p. Also chromenes 5 and 6 were obtained in good yield via reaction of compound 3 with salicyladehyde under different condition. The chromene derivatives 5 and 6 were further reacted with malononitrile in NH4OAc, afford the corresponding chromenopyridones 7 and 8. The structures of the synthesized compounds 3-8 were confirmed by analytical and spectral data. Compounds 4d, 4e, 5 and 6 showed higher anticancer activity against EAC cell line with IC50 values (75.32, 20.77, 73.1 and 67.05 µM) compared to doxorubicin as positive control with IC50 value (68.13 µM), moreover, these compounds showed potent activity on HEPG2 cell line with IC50 values (26.5, 19.2, 39.3, 44.9 µM), respectively, compared to doxorubicin (CAS 29042-30-6) (38.46 µM) and their activity increased synergistically when combined with γ-radiation.