Fourteen novel 4-(5-amino-4-cyano-1,3-oxazol-2-yl)benzenesulfonamides have been designed, synthesized, and characterized by spectroscopy and spectrometry methods. They have also been investigated on the NCI-60 cancer cell lines. The most activity compounds, 2, 3, and 9, in concentration 10 µM demonstrated mean GI50 values of 77, 70, and 68%, respectively, against the tumor cells. The best activity compound 2 showed the following GI50 values: non-small cell lung cancer (HOP-92) - 4.56 µM, breast cancer (MDA-MB-468) - 21.0 µM, melanoma (SK-MEL-5) - 30.3 µM. Besides, this compound indicates low toxicity with TGI and LC50 values >100 µM against all cancer cell lines. The COMPARE analysis (NCI) of compound 2 showed a very high correlation (r=0.91) with Tamoxifen as a selective estrogen receptors modulator. Molecular docking studies of ligand 2 demonstrated the complexation with estrogen receptors as a possible antitumor mechanism. The ADMET analysis of compound 2 indicates an optimistic prediction as an antitumor agent.

Novel 2,4-disulfonylsubstituted 5-aminothiazoles were synthesized and their anticancer activity was assessed at a high dose (10 μM) against NCI 60 cancer cell lines. Compounds 24 and 25 showed the antiproliferative activity with mean growth inhibition about 66.0%. Replacing 4-hydroxypiperidine 24 with the more hydrophilic N-methyl piperazine 25 increased the number of sensitive cell lines while replacing these hydrophilic groups with lipophilic ones abolished the anticancer activity. The COMPARE analysis showed that the tested compounds had a moderate positive correlation with alkylating agents (CCNU and methyl CCNU) and with a purine nucleotide biosynthesis inhibitor analog (L-cysteine). The results indicate that the above mechanisms of antitumor action of standard compounds are not the main ones for the tested compounds due to the lack of a high correlation. The results of this study allow us to consider compounds 24 and 25 as a basis for their further functionalization to obtain more active compounds.

Five imidazo[1,2-c]pyrimidine and pyrimido[1,6-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiproliferative activity and cytotoxicity. Primary bioassays in vitro showed that two of five synthesized compounds, 6-benzyl-8-(methylsulfonyl)-2,6-dihydroimidazo[1,2-c]pyrimidin-5(3H)-one, and 9-(methylsulfonyl)-7-propyl-2,3,4,7-tetrahydro-6H-pyrimido[1,6-a]pyrimidin-6-one possessed potent antiviral activity against BKV (EC50: 0.66 μM and 0.96, respectively). The selectivity index of these compounds is similar to that of cidofovir. Although antiviral activity was evident in secondary assays, significant virus inhibition occurred at or near the cytotoxic concentration (SI90=1). Here we show that substituted pyrimidine derivatives are a promising structure class of chemical compounds for the development of antiviral drugs against BKV infections. Hence these compounds may be taken as lead compounds for further development of novel antimicrobial and anticancer agents.