Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides

Yadav, Yogesh; Sharma, Deepti; Kaushik, Kumar; Kumar, Vineet; Jha, Amitabh; Prasad, Ashok K.; Len, Christophe; Malhotra, Sanjay V.; Wengel, Jesper; Parmar, Virinder S.

Blue and red arrows indicate the NOESY and HMBC cross peaks, respectively. The anticancer and toxicity of compounds 5a-e and 6a-e were evaluated by using the National Cancer Institute s 60 human cancer cell lines. Compounds 5a-e, where the sugar is attached to N-1 of the pyrazole ring, were found to be inactive against all the cell lines irrespective of the substituent on the aromatic ring. In the other series, compounds 6a, 6b, and 6c with 4-methyl, 4-methoxy, and 4-fluoro substituents, respectively, at the aromatic ring were also inactive. However, compounds 6d and 6e with 4-chloro and 4-bromo substituents at the aromatic ring, respectively, showed inhibition against multiple anticancer cell lines. The GI 50 (cytostatic parameter) and LC 50 (toxicity parameter) values of 6d and 6e for the selected cell lines are given in Table 5 . Compound 6d showed inhibition in 19 cell lines, and was most active against the renal cancer cell line UO-31 and breast cancer cell line HS 578T with GI 50 < 20 µM in both cases. The most active compound was 6e, which showed moderate inhibition in 39 cell lines. It showed significant inhibition against lung cancer cell line Hop-92 with a GI 50 of 9.3 µM and breast cancer cell line HS 578T with a GI 50 of 3.0 µM. Most importantly, both compounds (6d and 6e) did not show any toxicity, even at the highest concentration tested, as indicated by their high LC 50 values.