2. Academic Validation
  3. In silico ADMET analysis of the A-, B- and D-modified androstane derivatives with potential anticancer effects

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.
Tijana Lj Šestić 1,  Jovana J Ajduković 2,  Maja A Marinović 3,  Edward T Petri 3,  Marina P Savić 1
Affiliations

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: [email protected].
  • 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.

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