Design, Synthesis, Anticancer Screening and Virtual Analysis of New 7-Sulfonyldiazepan- and 7-Sulfonylpiperazine-substituted Oxazolo[4,5-d]pyrimidines

The design of novel anticancer agents has been advanced by applying machine learning techniques, leading to several classification and regression structure-activity relationship models specifically tailored for the human glioblastoma SNB-75. Using these models, a virtual library was screened to identify compounds with potential activity against the SNB-75 cell line. A series of new 7-sulfonyldiazepan- and 7-sulfonylpiperazine-substituted oxazolo[4,5-d]pyrimidines were synthesized and evaluated for their antitumor activity against the NCI-60 cell lines. 7-[4-(Benzenesulfonyl)piperazin-1-yl]-2-(4-methylphenyl)-5-phenyl[1,3]oxazolo-[4,5-d]pyrimidine demonstrated cytotoxic activity and a high level of selectivity to CNS SNB-75, while 2-(4-methylphenyl)-7-(4-methylsulfonyl-1,4-diazepan-1-yl)-5-phenyl[1,3]oxazolo[4,5-d]pyrimidine showed very high activity against the non-small lung cancer NCI-H460 cell line. The compounds met drug-like criteria according to ADMET analysis. Molecular docking investigations of synthesized compounds demonstrated complex formation with carbonic anhydrase XII as a potential mechanism. This makes these compounds attractive for further study as agents against non-small cell lung cancer and CNS cancer.