The condensed 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole scaffold, combining indole and 1,2,4-triazole pharmacophores, represents a promising source of anti-inflammatory, antimicrobial and anticancer agents. In silico assessment of their toxicity, pharmacokinetics and molecular properties provides a rational basis for synthesis and biological evaluation.

The aim of this study is to apply in silico approaches to investigate the physicochemical, pharmacokinetic and toxicological properties of 1,2,4-triazolo-[1′,5′:1,6]pyrido[3,4-b]indole derivatives and to explore their potential as multitarget agents through molecular docking.

Materials and methods. The pharmacological properties of 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole derivatives were evaluated using in silico modeling approaches. Toxicity prediction was performed with the US EPA TEST software package, while physicochemical and pharmacokinetic parameters were assessed using SwissADME. Molecular docking was conducted to analyze ligand interactions with cyclooxygenase-2, lanosterol 14α-demethylase, peptide deformylase of E. coli and S. aureus and anaplastic lymphoma kinase.

Results. The 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole derivatives were characterized by moderate oral toxicity and low mutagenic risk, except for compounds 1 and 5. Drug-likeness analysis confirmed compliance with criteria for orally active agents, while ADME modeling indicated high gastrointestinal absorption, limited central nervous system penetration (except compound 10) and potential CYP450 interactions. Docking studies revealed strong binding to COX-2 and CYP51, with compounds 2, 5, 8 and 10 showing affinities comparable to fluconazole. Several derivatives also exceeded actinonin in binding to E. coli peptide deformylase and displayed diverse interactions with S. aureus PDF. Compounds 2, 5 and 10 demonstrated binding energies against ALK close to crizotinib.

Overall, these findings suggest favorable pharmacokinetic profiles and multitarget potential for anti-inflammatory, antimicrobial and anticancer applications, with lipophilicity and CYP450 interactions identified as possible limitations.

Conclusions. In silico modeling demonstrated that 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole derivatives possess favorable pharmacokinetic properties, relatively low predicted toxicity, and strong affinities toward multiple pharmacologically relevant targets. These findings provide a rationale for further experimental validation and the development of novel multitarget drug candidates.