Synthesis and QSAR studies of 16-(3-methoxy-4-substituted benzylidene) androstene derivatives as anticancer agents

In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antipoliferative activity against cancer cells and developing their QSAR models, a series or 16-(3-methoxy-4-substituted benzylidene)androst-5-ene derivatives have been synthesized. The selected compounds are evaluated for antineoplastic activity against a panel or three human cell lines-breast. CNS and lungs at NCI, Bethesda, USA. The results presented herein indicate that compound 15-18, 21, 22, 25-30 are active anticancer agents. The QSAR investigation with multiple linear regression analysis has been applied to find a correlation between different calculated physicochemical parameters of these compounds and biological activity. Application of datasets by using CODESSA software has led to QSAR equations based on the 3 descriptors. The significant QSAR models have been obtained with R-2 values which range from 0.9692-0.8225 and good predictive performance (q(2) range: 0.9264-0.7121). These models are expected to be useful for the anticancer screening or androstene derivatives having substitution at position 3, 16 and 17 asteroid nucleus.