1,3,4-thiadiazole derivatives as PI3Ks inhibitor: design, in silico studies, synthesis, characterization, and antimicrobial evaluation

Since PI3Ks are targeted by a variety of bacterial pathogens, they represent a promising target for host-directed immune therapy and may be beneficial in managing persistent bacterial infections. In the present study, computational studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives for phosphoinositide-3-kinases (PI3Ks) inhibitors were carried out using dock scores, Glide scores, and the MMGBSA dG method, with comparison to standard drugs (ofloxacin and fluconazole). A series of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives (D1-D17) were synthesized and evaluated for their in vitro antimicrobial activity against both gram-positive and gram-negative bacterial strains, as well as fungal strains, using the tube dilution method. The synthesized compounds were characterized based on their physicochemical properties, and spectral data confirmed consistency with the proposed molecular structures. Docking studies, the MMGBSA analyses, and in vitro antimicrobial activity results indicated that compounds D₄, D₆, D₈, and D₁₂ were the most active against different microbial species and also showed favorable docking results in comparison with the PDB ligand and standard antimicrobial drugs (ofloxacin and fluconazole). This study highlights the potential of these compounds for future in vivo antimicrobial and anticancer investigations.