In silico ADMET analysis of the A-, B- and D-modified androstane derivatives with potential anticancer effects

Tijana Lj Šestić; Jovana J Ajduković; Maja A Marinović; Edward T Petri; Marina P Savić

doi:10.1016/j.steroids.2022.109147

In silico ADMET analysis of the A-, B- and D-modified androstane derivatives with potential anticancer effects

Steroids. 2023 Jan:189:109147. doi: 10.1016/j.steroids.2022.109147. Epub 2022 Nov 18.

Authors

Tijana Lj Šestić¹, Jovana J Ajduković², Maja A Marinović³, Edward T Petri³, Marina P Savić¹

Affiliations

¹ Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
² Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: jovana.ajdukovic@dh.uns.ac.rs.
³ Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia.

PMID: 36410412
DOI: 10.1016/j.steroids.2022.109147

Abstract

The major challenge in the fight against cancer is to design new drugs that will be more selective for cancer cells, with fewer side effects. Synthetic steroids such as cyproterone, fulvestrant, exemestane and abiraterone are approved powerful drugs for the treatment of hormone-dependent diseases such as breast and prostate cancers. Therefore, androstane derivatives in 17-substituted, 17a-homo lactone and 16,17-seco series, with potent anticancer activity, were selected for pharmacokinetic and druglike predictions from the absorption, distribution, metabolism and excretion (ADME) models. In silico determination of physico-chemical and ADMET properties was performed using SwissADME and ProTox-II web tools. The possibility of gastrointestinal absorption and brain penetration was analyzed using the BOILED-Egg model, while the in silico evaluation of the similarities between selected steroid derivatives and FDA-approved drugs was carried out using the SwissSimilarity tool. Of all tested, two compounds that showed good in silico ADMET results, in addition to promising cytotoxicity and molecular docking results, could potentially be evaluated in in vivo tests.

Keywords: 16,17-seco; 17a-homo lactone; 17α-picolyl; Androstane derivatives; Computational chemistry; Pharmacokinetic prediction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androstanes / chemistry
Androstanes / pharmacology
Antineoplastic Agents* / chemistry
Brain
Humans
Male
Molecular Docking Simulation
Prostatic Neoplasms* / drug therapy
Steroids / chemistry

Substances

Androstanes
Steroids
Antineoplastic Agents