Browsing by Author "Ullah, Hayat"

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Design, synthesis, in vitro urease inhibitory potentials and in silico molecular docking study of benzimidazole bearing thiosemicarbazides/ sulfonamide Analogues
(Elsevier, 2023-10) Alzahrani, Abdullah Yahya Abdullah; Adalat, Bushra; Ullah, Hayat; Taha, Muhammad; Othman, Mohamed S; Fareid, Mohamed A; Khaled, Azza M; Rahim, Fazal
The nickel-containing urease enzyme is responsible for the pathogenesis of hepatic coma, hepatic encephalop- athy, urolithiasis, gastric and peptic ulcer. These enzymes also have a negative effect on the efficacy of soil nitrogen to produce crops. The urease enzyme inhibitors may be thought as a strategy for reducing the negative effects of ureolytic bacteria. The present study involves a novel approach to the synthesis benzimidazole thio- semicarbazides and sulphonamide derivatives as potent urease inhibitor. All the analogues exhibited good in- hibition potential. Among the thiosemicarbazides series, the most potent were analogs 1 g and 1 h having an IC50 = 2.40 ± 0.10 and 3.10 ± 0.10 µM respectively. Among the sulphonamide series, the most potent analogs were 2f and 2j having an IC50 = 3.90 ± 0.10 and 1.40 ± 0.001 µM respectively. Structure activity relationship study shows that among the two series, the most potent analogs were those having electron-withdrawing groups. Molecular docking study was carried out to check the interactions between the synthesized compounds and the urease enzyme’s active sites. Furthermore, to evaluate the stability of the most active compound in complex with the urease enzyme a total of 200 ns MD simulation was carried out. The MD simulation study revealed that the compound formed a more stable complex with the urease enzyme and remained stable throughout the 200 ns MD simulation. All Compounds were verified for cytotoxicity against 3T3 mouse fibroblast cell line and detected nontoxic.
Investigation of novel benzimidazole-based indole/thiazole hybrids derivatives as effective anti-diabetics and anti-alzheimer’s agents: Structure-activity relationship insight, in vitro and in silico approaches
(Elsevier B.V., 2024-05) Naz, Haseena; Othman, Mohamed S; Rahim, Fazal; Hussain, Rafaqat; Khan, Shoaib; Taha, Muhammad; Hafez, Mohamed M; Abdel-Hafez, Lina JM; Ullah, Hayat; Khan, Ihsan Ullah; Khan, Yousaf; Shah, Syed Adnan Ali
Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are common in developed countries and their incidence is increasing. The research is mostly concentrated on the exploration of novel therapies to remedy or avert these ailments. AD and T2DM have several molecular pathways in common that contributes to their degenerative development. A novel series of ten hybrid analogues (1–10) based on benzimidazole bearing indole analogues were synthesized and these scaffolds were characterized by spectroscopic techniques like HR-EIMS, 13CNMR and 1 HNMR. Furthermore, the synthesized moieties were screened for α-amylase and α-glucosidase inhibitory activities. All these synthesized analogues showed good to moderate α-amylase and α-glucosidase inhibition potency ranging (4.90 ± 0.10 to 15.30 ± 0.60 µM) and (5.30 ± 0.10 to 16.10 ± 0.60 µM) while acarbose was used as a reference standard (IC50 = 10 0.30 ± 0.20 µM), (IC50 = 9.80 ± 0.20 µM). Another series of ten hybrid analogues (11–20) based on benzimidazole bearing thiazole moieties were synthesized and were evaluated for AChE and BuChE inhibition activities. All these newly afforded analogues showed good to moderate AChE and BuChE inhibitory potential ranging of (IC50 = 0.20 ± 0.01 µM), (IC50 = 0.15 ± 0.01 µM) to (IC50 = 3.90 ± 0.20 µM), (IC50 = 3.80 ± 0.10 µM) while Donepezil was taken as a reference standard with (IC50 = 0.016 ± 0.01 µM), (IC50 = 0.30 ± 0.010 µM).The scaffolds were also characterized using spectroscopic techniques such as HR-EIMS, 13CNMR and 1 HNMR for a better understanding of their structure. SAR was done for all synthesized analogues for substituents.In addition, docking research was conducted to determine the binding mode of interaction between the active site of analogues and targeted enzymes. This work aims to estimate the potential of the synthesized scaffolds as competitors to existing drugs. Incorporating molecular docking analysis with in vitro activities improves the accuracy of predictions and validates the possibility of these compounds as options for treating type-2 diabetes and Alzheimer’s disease.
New Cholinesterase inhibitors based on 1,2,4-triazole bearing benzenesulfonohydrazide skeleton: Synthesis, in vitro and in silico studies
(Elsevier B.V, 2024-08) Othman, Mohamed S; Naz, Haseena; Rahim, Fazal; Ullah, Hayat; Hussain, Rafaqat; Taha, Muhammad; Khan, Shoaib; Fareid, Mohamed A; Aboelnaga, Shimaa M; Altaleb, Anas T; Iqbal, Rashid; Shah, Syed Adnan Ali
We have synthesized 1,2,4-triazole bearing benzenesulfonohydrazide analogues (1–21), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and were evaluated against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes. All the newly synthesized analogues showed excellent to good inhibition potential with IC50 values ranged from 0.30 ± 0.050 to 15.21 ± 0.50 µM (against AChE) and 0.70 ± 0.050 to 18.27 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Analogues 2 and 4 which were found inactive against these enzymes. However, analogues 17 (IC50 = 0.30 ± 0.050 and 0.70 ± 0.050 µM) and 13 (IC50 = 0.70 ± 0.05 and 1.70 ± 0.050 µM) were found to have potent inhibitory potentials against the targeted enzymes. Structure-activity relationship was carried out which mainly depends upon the nature, position and numbers of the substitution present on phenyl rings that may be electron withdrawing/donating. Molecular docking study was carried out to know about the binding mode of interaction of the most active site of the synthesized analogues with the targeted enzymes.
Synthesis, in vitro biological evaluation and in silico molecular docking study of hydroxy‑quinoline based sulfonohydrazide derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors
(Elsevier, 2024-02) Alzahrani, Abdullah Yahya Abdullah; Ullah, Hayat; Rahim, Fazal; Khan, Fahad; Wadood, Abdul; Taha, Muhammad; Al-Bagawi, Amal; Fareid, Mohamed; Othman, Mohamed S
A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures were elucidated by using various spectroscopic tools including 1 HNMR, 13CNMR and HREI-MS and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives showed the varied range of AChE and BuChE activities having IC50 values ranging from 0.20 ± 0.01 to 11.60 ± 0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug Donepezil (IC50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10 were identified to be most potent, even more, active than standard drug having IC50 values of 0.40 ± 0.05, 0.20 ± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE) respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to investigate the mechanism of interactions between the scaffolds that are most active and the active sites of specific AChE and BuChE enzymes.