In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC50 values in the range of 3.2 ± 0.3–185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents.
In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H-NMR, 13C-NMR, ESI–MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC50 value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors.
The development of new antidiabetes agents is necessary to obtain optimal glycemic control and overcome its complications. Different quinazolin-4(3H)-one bearing phenoxy-acetamide derivatives (7a–r) were designed and synthesized to develop α-glucosidase inhibitors. All the synthesized derivatives were evaluated against α-glucosidase in vitro and among them, compound 7b showed the highest α-glucosidase inhibition with an IC50 of 14.4 µM, which was ∼53 times stronger than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compound 7b was a competitive type towards α-glucosidase. Also, molecular docking studies analyzed the interaction between the most potent derivative and α-glucosidase. Current findings indicate the new potential of quinazolin-4(3H)-ones that could be used for the development of novel agents against diabetes mellitus.
In this work, novel anti‐α‐glucosidase agents, thieno[2,3‐b]quinoline‐acetamide derivatives 5 a–m have been designed and synthesized. These compounds were evaluated in vitro against yeast α‐glucosidase. Most of the title new compounds exhibited a significant α‐glucosidase inhibitory activity in comparison to positive control, acarbose. In this regards, the most potent compound amongst the tested compounds, compound 5 k, with IC50=48.66±0.02 μM was 15.6‐fold more potent than acarbose. Compound 5 k was a competitive inhibitor into α‐glucosidase and interacted with important residues of the active site of this enzyme. Three most potent compounds among the newly synthesized compounds 5 j–k and 5 m were evaluated in silico in term of the oral druglikeness and pharmacokinetic properties. The obtained results predicted that these compounds had satisfactory oral druglikeness and pharmacokinetic properties.
In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors.
To identify potent urease inhibitors, in the current study, a series of thioxothiazolidinyl-acetamides were designed and synthesized. The prepared compounds were characterized by spectroscopic techniques, including FTIR, 1HNMR, 13CNMR, and elemental analysis. In the enzymatic assessments, it was demonstrated that all derivatives had significant urease inhibition with IC50 values in the range of 1.473–9.274 µM in comparison with the positive control hydroxyurea (IC50 = 100.21 ± 2.5 µM) and thiourea (IC50 = 23.62 ± 0.84 µM). Compound 6i (N-benzyl-3-butyl-4-oxo-2-thioxothiazolidine-5-carboxamide) was the most active agent with an IC50 value of 1.473 µM. Additionally, kinetic investigation and in silico assessments of 6i was carried out to understand the type of inhibition and behavior of the most potent derivative within the binding site of the enzyme. Noteworthy, the anti-urease assay against P. vulgaris revealed 6e and 6i as the most active agents with IC50 values of 15.27 ± 2.40 and 17.78 ± 3.75 µg/mL, respectively. Antimicrobial evaluations of all compounds reveal that compounds 6n and 6o were the most potent antimicrobial agents against the standard and resistant S. aureus. 6n and 6o also showed 37 and 27% inhibition in the development of biofilm by S. aureus at 512 µg/ml. Furthermore, the MTT test showed no toxicity up to 100 µM. Taken together, the study suggests that the synthesized thioxothiazolidinyl-acetamides bases derivatives may serve as potential hits as urease inhibitors.
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