Local QSAR modeling of cytotoxic activity of newly designed androstane 3-oximes towards malignant melanoma cells

Abstract

As one of the deadliest forms of skin cancers, malignant melanoma is the most common cause of death from this type of cancer. Malignant melanoma has a steadily increasing incidence and the medical treatment options are still quite limited. One of the possible options for malignant melanoma treatment is medication therapy. The present study is focused on the development of new compounds that can be possibly used for malignant melanoma treatment. A newly synthesized series of alkylaminoethyl derivatives of androstane 3-oximes expressed significant cytotoxic activity towards malignant melanoma cells. This was an excellent basis for the development of quantitative structure-activity relationship (QSAR) models for the prediction of cytotoxic activity of not yet synthesized compounds. Also, on the basis of the cytotoxic activity data the molecular docking and molecular dynamics analysis were carried out. This local QSAR modeling, which is based on a limited set of structurally similar compounds, resulted in one univariate linear regression model, four multiple linear regression models and five support vector machines models. All of the models were confirmed to be statistically reliable with quite good prediction ability. The results of comparative molecular docking and molecular dynamics analysis indicated a high binding potential of novel compounds in regards to cisplatin as well-known chemotherapy drug. The established QSAR models and the results of molecular docking and molecular dynamics can be considered to be the guidelines for the design of new compounds worth synthesizing as potential lead compounds for malignant melanoma treatment.