Bridging Experiment and Computation: In Silico Admet, Protox-III, and Target-Guided Docking of Nitro-Substituted Dichlorodiazadienes
- DOI
- 10.2991/978-94-6239-668-5_8How to use a DOI?
- Keywords
- dichlorodiazadiene; ADMET-AI; ProTox-III; molecular docking
- Abstract
This study integrates experimental findings with computational analysis to elucidate the pharmacokinetic, toxicological, and molecular interaction profiles of six nitro-substituted dichlorodiazadiene derivatives. Comprehensive ADMET modeling using ADMET-AI and vNN-ADMET revealed high oral absorption (HIA ≈ 1.0) and strong plasma protein binding, accompanied by moderate CYP1A2 and CYP2C19 inhibition and acceptable excretion kinetics. ProTox-III predictions classified the compounds within GHS toxicity classes 3–4 (LD₅₀ = 90–710 mg/kg), highlighting mutagenicity, carcinogenicity, and cardiotoxicity as key structural liabilities linked to nitro- and azo-functionalities. Among the evaluated molecules, Compounds 1 and 2 exhibited comparatively safer profiles, whereas Compounds 3 and 4 showed acute toxicity and genotoxic potential. Molecular docking simulations performed with SwissDock (AutoDock Vina engine) identified FabH (4IJ0) as the preferential binding target of Compound 4 (ΔG = − 4.987 kcal/mol) compared with GyrB (2XCT) (ΔG = − 3.850 kcal/mol). The binding network involved hydrogen bonding, π–π stacking, and halogen interactions that rationalize the experimentally observed antibacterial potency. Overall, the integrated ADMET–toxicity–docking workflow underscores FabH inhibition as a plausible mechanism of action and provides a predictive framework for structure-guided optimization of safer, more selective dichlorodiazadiene analogues.
- Copyright
- © 2026 The Author(s)
- Open Access
- Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.
Cite this article
TY - CONF AU - Gulnar Atakishiyeva AU - Nigar Ahmedova AU - Sevinc Mukhtarova AU - Ayten Niyazova AU - Namiq Shikhaliyev AU - Abel Maharramov PY - 2026 DA - 2026/05/14 TI - Bridging Experiment and Computation: In Silico Admet, Protox-III, and Target-Guided Docking of Nitro-Substituted Dichlorodiazadienes BT - Proceedings of the International Conference on Current Problems in Engineering and Applied Sciences (ICCPEAS 2025) PB - Atlantis Press SP - 64 EP - 83 SN - 2352-5401 UR - https://doi.org/10.2991/978-94-6239-668-5_8 DO - 10.2991/978-94-6239-668-5_8 ID - Atakishiyeva2026 ER -