Computer-aided docking combined with AlphaFold-based protein modeling revealed strong binding affinities of the ligand DOLA ((Z)-5-(dimethylamino)-N-(octadec-9-en-1-yl)naphthalene-1-sulfonamide) to metabolic proteins in the insect species Tenebrio molitor, Tribolium castaneum, Locusta migratoria, Lucilia cuprina, and Drosophila melanogaster. Significant interactions were observed with cytochrome P450 families CYP6 and CYP4 involved in detoxification, hormone regulation, and fatty acid metabolism, with binding energies ranging from −10.4 to −8.5 kcal/mol. DOLA also showed affinity for enzymes related to fatty acid metabolism and transport, including long-chain fatty acid-CoA ligase, fatty acyl-CoA reductases, CYP18a1, lipocalins, and fatty acid desaturases. These in silico findings highlight DOLA as a promising ligand for studying insect metabolic pathways and as a potential agent for population control, warranting further experimental validation.

The search for new antibacterial drugs has continued to be an urgent matter. One of the approaches is the development of covalent inhibitors using biochemoinformatics at the initial stages. In this work, structures of a few plant-derived substances with electrophilic unsaturated carbonyl and structures of small synthetic compounds suitable for fragment-based drug discovery (FBDD) with -CH₂-Br group were selected as ligands for sets of structures of bacterial proteins. The theoretical assessment was carried out using the Autodock Vina program for calculation and FYTdock for the organization of the process and the analysis of results. Natural Ixerine D as well as synthetic 4-(4-(2-bromoethyl)piperazin-1-yl)-7-nitrobenzofurazan demonstrated the most promising results as potential Cys-targeted inhibitors.

Zn-containing proteins play essential roles in the viability and virulence of bacteria, so are considered to be possible molecular new drug targets. Based on literature data about N-acyl-o-phenylenediamine and 2-pycolylamine as warheads of drugs and molecular probes for Zn-bearing enzymes like histone deacetylases, we guessed that N-(7-nitrobenzofurazan-4-y)-o-phenylenediamine (NBD-OPD), 2-pycolyl-(N-(7-nitrobenzofurazan-4-amine)) and ciprofloxacin 2-pycolylamide (CPF-Pic2) are potential fluorescent inhibitors of such enzymes. Molecular docking was performed for estimate affinity of the compounds to a set of bacterial enzymes, and photochemical and electrochemical properties were calculated in silico using DFT.

Developing novel insecticidal agents is critical to address the rising resistance to conventional chemical classes. Using AutoDock Vina, this study screened six xanthene derivatives (Resuc, Resaze, Resac, Resfac, Reshex, and Resaba) against sensory, metabolic, and transport proteins associated with fatty acid pathways from four insect genera (Leptinotarsa, Locusta, Lucilia, and Drosophila). Resfac exhibited the strongest binding score for cuticular protein A0A3Q8HFR0 (−11.4 kcal/mol) and cytochrome P450. Resaze displayed broad interaction patterns across 29 targets (−10.5 to −9.0 kcal/mol). Resac, Resuc, Reshex, and Resaba showed varied binding preferences for odorant and chemosensory proteins. These preliminary findings indicate the prospective application of xanthene scaffolds as functional building blocks for designing targeted insect control tools or molecular probes.

Docking calculations in semi-automatic virtual screening mode have been performed using AutoDock Vina (5 × 5 × 5 nm grid box, centered on the chain A) and FYTdock helper software. N-hexanoyl ciprofloxacin has been found to bind with chitinases from Ostrinia furnacalis (pdb codes: 7vrg, 6jaw, 6jay, 6jmn, 5y2b; energy of bindings (Ebind) −10.2…−9.7). N-hexanoyl-N’-NBD-piperazine, and NpipHex bind in silico with the enzyme less effectively (pdb codes: 6jaw, 5y2b, 6jay, 5y2c, 3wkz; Ebind −9.3…−8.9). Lipid-like N-NBD-oleylamine and N-Dansyl-oleylamine demonstrated quite similarly, but smaller affinity (Ebind −8.6…−8.0). Examples of interactions close to the active sites of the chitinases were found for all compounds. These results provide new insights into insect biochemistry of chitinases showing new molecular scaffolds suitable as prototypes of tools for pest control or fluorescence-based screening.