In silico evaluation of drug-likeness properties of steroidal semicarbazones and steroidal oxazolo[4.5-b]quinoxalines

3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 485-488) 

 

АУТОР(И) / AUTHOR(S): Marijana B. Živković, Sandra Šegan, Dušan M. Sladić

 

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DOI:  10.46793/ICCBIKG25.485Z

САЖЕТАК / ABSTRACT:

Antibiotic resistance is accelerating at an alarming rate, emerging as a major global threat with the potential to undermine nearly a century of therapeutic progress. Consequently, the scientific community is investing considerable effort into the discovery of novel antimicrobial agents. In this study, the in silico drug-likeness of steroidal semicarbazones (SCs) with varying C- 17 substituents and their corresponding oxazolo[4.5-b]quinoxalines (Qxs) was assessed using publicly available online platforms ‒ Molinspiration, preADMET, and pkCSM. According to Lipinski’s Rule of Five (Ro5), all compounds, except the cholestane-based Qx, meet the drug- likeness criteria. Functionalization of SCs into Qxs resulted in a marked increase in lipophilicity (by more than two units) and further reduced already low water solubility, thereby causing Qxs to violate Ro5. Nevertheless, the Qxs demonstrated excellent predicted pharmacokinetic properties, including maximal predicted intestinal absorption (IA=100%), favorable steady-state volume of distribution (VDss > 0.44, log L/kg), and limited blood–brain barrier (BBB) permeability. Notably, the androstene- and progesterone-based Qxs exhibited reduced BBB permeability compared to their parent SCs, suggesting a potentially lower risk of neurotoxicity.

The obtained results indicate that drug-like steroidal Qxs may serve as promising candidates for synthesis and further evaluation of antimicrobial activity.

КЉУЧНЕ РЕЧИ / KEYWORDS:

Lipinski’s Rule of Five (Ro5), ADMET prediction, computational pharmacokinetics, in silico drug-likeness, oxazolo[4,5-b]quinoxalines

ПРОЈЕКАТ / ACKNOWLEDGEMENT:

This research is funded by the Ministry of Science, Technological Development and Innovation, Republic of Serbia, Grant No. 451-03-136/2025-03/200026.

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