Synthesis, characterization, computer-aided docking studies, and anti-fungal activity of two-armed quinazolin-2,4‑dione derivatives

•A new series of two-armed quinazolin-2,4-diones incorporating N-heterocyclic moieties 2–7 was synthesized.•The newly synthesized compounds were identified in the basis of melting point, elemental analyses, and spectral data.•The two-armed quinazolin-2,4-diones were investigated in vitro for their antifungal activities against Candida albicans.•Three most potent compounds 1, 3, and 4 exhibited noted inhibitory effects.•The molecular docking simulation was performed against sterol 14-alpha demethylase.•The eight compounds exhibited good ADMET profile and satisfied the Lipinski rule of drug likeness. A new series of two-armed quinazolin-2,4-diones incorporating N- heterocyclic moieties such as β-lactam, piperidine and/or morpholine, 2-thioxo imidazolidin-4-one and 2-iminothiazolidin-4-one 2–7 were designed and synthesized as attractive anti-fungal scaffolds. The structural elucidation of newly compounds was performed by means of FT-IR, 1H NMR, 13C NMR and MS techniques. Subsequently, the newly synthesized compounds were screened for their antifungal activity against Candida albicans via measuring the inhibition zone diameter around the fungal growth. The results obtained revealed varied response activity toward the tested fungal pathogen. Three most potent compounds 1, 3, and 4 exhibited noted inhibitory effects. Since, there was found superiority of the compound 1 in terms of inhibition zone diameter (mm) about the standard drug (i.e. Amphotericin B). Additionally, the MIC value was assessed for the potent compounds using different concentrations (5–400 μg/mL). A significant MIC value (20 μg/mL) was recorded for compound 1. Moreover, the molecular docking simulation was performed against sterol 14-alpha demethylase. In particular, compound 1 exhibited the best binding profile among the synthesized compounds (- 13.6 kcal/mol), followed by compounds 3 (-12.7 kcal/mol) and 4 (-11.9 kcal/mol). The structure activity relationship revealed the importance of electron withdrawing groups (chlorine atoms) on biological activity of compounds. Further, the eight compounds exhibited good ADMET profile and satisfied the Lipinski rule of drug likeness.