Synthesis, In Vitro Anti-Microbial Analysis and Molecular Docking Study of Aliphatic Hydrazide-Based Benzene Sulphonamide Derivatives as Potent Inhibitors of α-Glucosidase and Urease

Abstract

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.

Design, Synthesis, and Molecular Docking Studies of Integrated Benzylidenethiazolidine‐2,4‐Dione and Thieno[2,3‐d]pyrimidine‐6‐Carboxylate Derivatives as Potent Antidiabetic agents

“…4.54 (t, 2H, ester-O-CH 2 ), 7.15 (d, 2H,ArÀ H ), 7.49 (d, 2H, ArÀ H), 7.85 (s, 1H, benzylidene-=CH), 8.57 (s, 1H, pyrimidine-CH); 13 CNMR (100 MHz, CDCl 3 ):δ16.69, 40.68, 50.90, 61.52, 66.50, 116.59, 116.89, 120.37, 120.80, 123.36, 129.50, 132.40, 132.49, 133.13, 139.90, 154.19, 162.29, 163.58, 166.07, 167.58, 169.49; LC-MS (Positive ion mode): m/z 529 (M + H) + for C 24 H 21 FN 4 O 5 S 2 . (9 e): Yield: 89 %; IR (KBr) ν (cm À 1 ) 3013 (ArÀ CÀ H), 2962 (CÀ H), 1701 (C=O), 1602 (ArÀ C=C), 1536 (C=N), 1439 (CÀ N), 1242 (CÀ O); 1 HNMR (400 MHz, CDCl 3 ): δ 2.78 (s, 3H, thiophene-CH 3 ), 3.51 (t, 4H, morpholine-N-(CH 2 ) 2 ), 3 (…”

“…For example, thienopyrimidine and thiazolidinediones are the important nitrogen-and sulfur-containing heterocyclic derivatives known as potential candidates for antidiabetic and anticancer activities. [3] Over the past two decades, various thiophene-fused pyrimidine scaffolds have been developed and synthesized as drug-like candidates for a variety of pharmacological applications, particularly as adenosine receptor ligands. [4,5] Further, since purine and pyrimidine bases are structural elements of double-stranded nucleic acids, many fused pyrimidines and purines have been considered for integration through medicinal chemistry approaches to design effective therapeutic agents.…”

Dysregulated Liver Metabolism and Polycystic Ovarian Syndrome

“…Previously, PCOS was considered a reproductive disorder affecting fertility. However, PCOS has since been reclassified as a metabolic disorder since insulin resistance (IR) is acknowledged as one of the key pathogens [ 3 , 4 ]. Patients with PCOS commonly have a high prevalence of obesity and IR [ 3 ], carrying an increased risk of metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease [ 5 , 6 ].…”

Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure–Activity Relationship, Kinetics Mechanism, and In Silico Studies

“…This research identified a few drug-based conjugates that would be the best pharmacological agents for the inhibition of the urease enzyme. 11,21,22 The nonsteroidal anti-inflammatory drugs (NSAIDs) and their derivatives, such as acetylsalicylic acid, ibuprofen, diclofenac, mefenamic acid, flurbiprofen, naproxen, and piroxicam, were investigated for their ability to exhibit a range of biological activities, including inhibiting enzymes like α-glucosidase, β-glucuronidase, α-amylase, and urease. 4,11,23−27 Our objective was to design and synthesize the conjugates that combine mefenamic acid and diclofenac with sulfa drugs, employing the multitarget approach that is gaining popularity among pharmaceutical chemists worldwide.…”

“…To prepare safe and secure urease inhibitors, a variety of sulfa drugs and NSAID derivatives have been thoroughly studied in the past decade (Figure ). This research identified a few drug-based conjugates that would be the best pharmacological agents for the inhibition of the urease enzyme. ,, The nonsteroidal anti-inflammatory drugs (NSAIDs) and their derivatives, such as acetylsalicylic acid, ibuprofen, diclofenac, mefenamic acid, flurbiprofen, naproxen, and piroxicam, were investigated for their ability to exhibit a range of biological activities, including inhibiting enzymes like α-glucosidase, β-glucuronidase, α-amylase, and urease. ,,− …”