A combined in vitro and in silico approach of thiadiazole based Schiff base derivatives as multipotent inhibitor: Synthesis, spectral analysis, antidiabetic and antimicrobial activity

Abstract

We have developed new thiadiazole-containing Schiff base derivatives and examined their ability to inhibit α-amylase and α-glucosidase. Among the members of series, analogue 1 showed excellent inhibitory potential (IC50 = 1.60 ± 0.20 and 2.40 ± 0.10 µM for α-amylase and α-glucosidase) as compare to standard Acarbose (IC50 = 5.30 ± 0.20 and 6.10 ± 0.10 µM). Trifluoromethyl substituted analogue-1 showed best properties because of hydrogen bond formation. Analogue 3 and 9 were also found potent against the target enzymes. All the compounds were investigated for their antibacterial and antifungal activity. Analogue 1, 3 and 9 exhibited bacterial inhibition of 42.3 %, 40.1 %, 38.2 %, and 36.5 %, respectively in contrast to streptomycin (44 %). Analogue 1, 4 and 9 exhibited excellent anti-fungal potency of 43.4, 31.9 and 34.3 %, respectively as compared to standard terinafine (50.6675 %). Scaffolds (1–12) were analyzed through HREI-mass spectrometry, 13C NMR, and 1H NMR. The functioning of active interacting residues for the enzymes was determined by molecular docking (MD), and it was found that thiadiazole bearing Schiff base derivatives could be considered suitable anti-diabetic drugs. ADMET and DFT analysis was also performed to determine stability, drug properties and electronic properties (electrophilic, nucleophilic, HOMO, LUMO) of the synthesized compounds.