RESUMEN
The current study involves the synthesis of Schiff bases based on 1,2,4-triazoles skeleton and assessing their α-amylase and α-glucosidase profile. Furthermore, the precise structures of the synthesized derivatives were elucidated using various spectroscopic methods such as 1H-NMR, 13C-NMR and HREI-MS. Using glimepiride as the reference standard, the in vitro α-glucosidase and α-amylase inhibitory activities of the synthesized compounds were evaluated in order to determine their potential anti-diabetic properties. All analogues showed varied range of inhibitory activity having IC50 values ranging from 17.09 ± 0.72 to 45.34 ± 0.03⯵M (α-amylase) and 16.35 ± 0.42 to 42.31 ± 0.09⯵M (α-glucosidase), respectively. Specifically, the compounds 1, 7 and 8 were found to be significantly active with IC50 values of 17.09 ± 0.72, 19.73 ± 0.42, and 23.01 ± 0.04⯵M (against α-amylase) and 16.35 ± 0.42, 18.55 ± 0.26, and 20.07 ± 0.02⯵M (against α-glucosidase) respectively. The obtained results were compared with the Glimepiride reference drug having IC50 values of 13.02 ± 0.11⯵M (for α-glucosidase) and 15.04 ± 0.02⯵M (for α-amylase), respectively. The structure-activity relationship (SAR) studies were conducted based on differences in substituent patterns at varying position of aryl rings A and B may cause to alter the inhibitory activities of both α-amylase and α-glucosidase enzymes. Additionally, the molecular docking study was carried out to explore the binding interactions possessed by most active analogues with the active sites of targeted α-amylase and α-glucosidase enzymes.
RESUMEN
The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including 1H NMR, 13C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC50 = 9.30 ± 0.20⯵M). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC50 = 5.10 ± 0.40⯵M to 29.80 ± 0.20⯵M). Analyzing the structure-activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC50 = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60⯵M, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC50 = 9.30 ± 0.20⯵M). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.
Asunto(s)
Inhibidores Enzimáticos , Indoles , Simulación del Acoplamiento Molecular , Tiazoles , Triazinas , Ureasa , Ureasa/antagonistas & inhibidores , Ureasa/química , Tiazoles/química , Tiazoles/farmacología , Relación Estructura-Actividad , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Triazinas/química , Triazinas/farmacologíaRESUMEN
The clinical significance of benzimidazole-containing drugs has increased in the current study, making them more effective scaffolds. These moieties have attracted strong research interest due to their diverse biological features. To examine their various biological significances, several research synthetic methodologies have recently been established for the synthesis of benzimidazole analogs. The present study aimed to efficiently and quickly synthesize a new series of benzimidazole analogs. Numerous spectroscopic techniques, including 1H-NMR, 13C-NMR, and HREI-MS, were used to confirm the synthesized compounds. To explore the inhibitory activity of the analogs against α-amylase and α-glucosidase, all derivatives (1-17) were assessed for their biological potential. Compared to the reference drug acarbose (IC50 = 8.24 ± 0.08 µM), almost all the derivatives showed promising activity. Among the tested series, analog 2 (IC50 = 1.10 ± 0.10 & 2.10 ± 0.10 µM, respectively) displayed better inhibitory activity. Following a thorough examination of the various substitution effects on the inhibitory capacity of α-amylase and α-glucosidase, the structure-activity relationship (SAR) was determined. We looked at the potential mechanism of how active substances interact with the catalytic cavity of the targeted enzymes in response to the experimental results of the anti-glucosidase and anti-amylase. Molecular docking provided us with information on the interactions that the active substances had with the various amino acid residues of the targeted enzymes for this purpose.
RESUMEN
A unique series of sulphonamide derivatives was attempted to be synthesized in this study using a new and effective method. All of the synthesized compounds were verified using several spectroscopic methods, including FTIR, 1H-NMR, 13C-NMR, and HREI-MS, and their binding interactions were studied using molecular docking. The enzymes urease and α-glucosidase were evaluated against each derivative (1-15). When compared to their respective standard drug such as acarbose and thiourea, almost all compounds were shown to have excellent activity. Among the screened series, analogs 5 (IC50 = 3.20 ± 0.40 and 2.10 ± 0.10 µM) and 6 (IC50 = 2.50 ± 0.40 and 5.30 ± 0.20 µM), emerged as potent molecules when compared to the standard drugs acarbose (IC50 = 8.24 ± 0.08 µM) and urease (IC50 = 7.80 ± 0.30). Moreover, an anti-microbial study also demonstrated that analogs 5 and 6 were found with minimum inhibitory concentrations (MICs) in the presence of standard drugs streptomycin and terinafine.