Mona M. Kamel

Synthesis and antitumor activity of novel 6-aryl and 6-alkylpyrazolo[3,4-d]pyrimidin-4-one derivatives

A series of new 6-arylpyrazolo[3,4-d]pyrimidin-4-ones and 6-alkylpyrazolo[3,4-d]pyrimidin-4-ones were synthesized. Some of the newly synthesized compounds were tested in vitro on human colon tumor cell line (HCT116). Most of the test compounds exploited potent antitumor activity, especially compound 10a which displayed the highest activity among the test compounds with IC(50) equal to 0.47 μg/mL.

Novel Thiophenes, Thienopyrimidines, and Triazolothienopyrimidines for the Evaluation of Anticancer and Augmentation Effects of γ-Radiation

New derivatives of thiophenes 2, 12, iminoaminothieno[2,3‐d]pyrimidines 3, 5, and 6, triazolothieno[2,3‐d]pyrimidines 8–11, pyrazolo‐ and triazinothieno[2,3‐d]pyrimidines 4, 7, respectively, have been prepared by different synthetic procedures. Structure elucidation of the newly synthesized compounds was carried out via elemental analyses and spectral data. The antitumor activity of compounds 2, 3, and 9–12 was evaluated against in‐vitro cell lines (HEPG‐2 and MCF‐7). Compounds 2, 3, 10, 11, and 12 showed significant in‐vitro cytotoxic activity against hepatocellular carcinoma (HEPG‐2) compared to the reference drug Doxorubicin. Compound 2 showed significant in‐vitro cytotoxic activity against breast cancer (MCF‐7) cells compared to the reference drug Doxorubicin. The augmenting effect of γ‐radiation was assessed; here, compounds 2, 3, 10, and 11 showed the most potent in‐vitro anticancer activity.

Synthesis and Anticancer Evaluation of 1,3,4-Oxadiazoles, 1,3,4-Thiadiazoles, 1,2,4-Triazoles and Mannich Bases

A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various secondary amines furnished the Mannich bases 6a-p. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against six human cancer cell lines and normal fibroblast cells. Sixteen of the tested compounds exhibited significant cytotoxicity against most cell lines. Among these derivatives, the Mannich bases 6j, 6m and 6p were found to exhibit the most potent activity. The Mannich base 6m showed more potent cytotoxic activity against gastric cancer NUGC (IC50=0.021 µM) than the standard CHS 828 (IC50=0.025 µM). Normal fibroblast cells WI38 were affected to a much lesser extent (IC50>10 µM).