22 results on '"Wadood, Abdul"'
Search Results
2. Chalcones: As Potent α-amylase Enzyme Inhibitors; Synthesis, In Vitro, and In Silico Studies
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Khan Momin, Iqbal Maryam, Wadood Abdul, Ashfaq Ur Rehman, Ali Mahboob, Rafique Rafaila, Zaman Khair, Alam Aftab, Shah Sana, Mohammed Khan Khalid, and Yousaf Muhammad
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chemistry.chemical_classification ,Chalcone ,biology ,Molecular model ,Stereochemistry ,Aryl ,Condensation reaction ,Molecular Docking Simulation ,Structure-Activity Relationship ,chemistry.chemical_compound ,Chalcones ,Enzyme ,chemistry ,Catalytic Domain ,Drug Discovery ,medicine ,biology.protein ,Computer Simulation ,Amylase ,Enzyme Inhibitors ,alpha-Amylases ,IC50 ,Acarbose ,medicine.drug - Abstract
Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-16) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Methods: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by Claisen-Schmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HRESI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-16) were synthesized, characterized, and evaluated for their α- amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.
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- 2021
3. Syntheses, in vitro evaluation and molecular docking studies of 5-bromo-2-aryl benzimidazoles as α-glucosidase inhibitors
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Arshad, Tanzila, Khan, Khalid Mohammed, Rasool, Najma, Salar, Uzma, Hussain, Shafqat, Tahir, Tehreem, Ashraf, Mohammed, Wadood, Abdul, Riaz, Muhammad, Perveen, Shahnaz, Taha, Muhammad, and Ismail, Nor Hadiani
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- 2016
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4. Synthesis, biological evaluation and molecular docking study of indazole based schiff base analogues as new anti-diabetic inhibitors.
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Taha, Muhammad, Gilani, Sadaf Jamal, Kazmi, Imran, Rahim, Fazal, Adalat, Bushra, Ullah, Hayat, Nawaz, Faisal, Wadood, Abdul, Ali, Zarshad, Shah, Syed Adnan Ali, and Khan, Khalid Mohammed
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SCHIFF bases , *MOLECULAR docking , *BINDING sites , *AZOLES , *STRUCTURE-activity relationships , *AMYLOLYSIS , *INDAZOLES - Abstract
• Synthesis of indazole based schiff base analogues. • Identification of a new class of α-glucosidase and α-amylase inhibitors. • Analogue 22 proved to be most active α-glucosidase and α-amylase inhibitors. • Docking study was conducted to interpret the obtained results. Indazole-based Schiff base analogues (1–27) were synthesized by a three-step reaction pathway starting from 1-methyl-1 H -indazole-3-carboxylic acid as the basic compound. The structure of the new indazoles was characterized and confirmed by mass spectral analyses as well as NMR spectroscopic data. All synthesized analogues were screened for their in vitro α-glucosidase and α-amylase inhibitory activities. All analogues of the series exhibited good inhibitory potentials, with IC 50 values ranging from 0.40 ± 0.01 to 16.20 ± 0.30 µM for α-glucosidase and 0.70 ± 0.01 to 17.40 ± 0.30 µM for α-amylase as compared to the standard drug acarbose (IC 50 = 12.90 ± 0.10 and 12.80 ± 0.10 µM, respectively). The most effective analogue of the series is analogue 22 having 3‑hydroxyl groups with an IC 50 value of 0.40 ± 0.01 µM and 0.70 ± 0.01 µM for α-glucosidase and α-amylase, respectively. Structure-activity relationship was carried out, which mainly depends upon the nature, number, position, and electron donating/withdrawing effect of the substituent(s) attached to the phenyl ring. To investigate the binding interaction of the potent analogue with the active site of an enzyme, molecular docking studies were carried out. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Schiff bases of tryptamine as potent inhibitors of nucleoside triphosphate diphosphohydrolases (NTPDases): Structure-activity relationship.
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Kanwal, Mohammed Khan, Khalid, Salar, Uzma, Afzal, Saira, Wadood, Abdul, Taha, Muhammad, Perveen, Shahnaz, Khan, Huma, Lecka, Joanna, Sévigny, Jean, and Iqbal, Jamshed
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TRYPTAMINE , *SCHIFF bases , *NUCLEOTIDES , *CHEMICAL synthesis , *NUCLEOSIDE triphosphatase - Abstract
Graphical abstract Highlights • Schiff bases of tryptamine were synthesized. NTPDase inhibitory activity of synthetic derivatives have been evaluated. • Kinetic study of the three lead compounds has been performed. • In silico study of the most active compound was also carried out against NTPDas-1. Abstract Overexpression of NTPDases leads to a number of pathological situations such as thrombosis, and cancer. Thus, effective inhibitors are required to combat these pathological situations. Different classes of NTPDase inhibitors are reported so far including nucleotides and their derivatives, sulfonated dyes such as reactive blue 2, suramin and its derivatives, and polyoxomatalates (POMs). Suramin is a well-known and potent NTPDase inhibitor, nonetheless, a range of side effects are also associated with it. Reactive blue 2 also had non-specific side effects that become apparent at high concentrations. In addition, most of the NTPDase inhibitors are high molecular weight compounds, always required tedious chemical steps to synthesize. Hence, there is still need to explore novel, low molecular weight, easy to synthesize, and potent NTPDase inhibitors. Keeping in mind the known NTPDase inhibitors with imine functionality and nitrogen heterocycles, Schiff bases of tryptamine, 1 – 26 , were synthesized and characterized by spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C NMR. All the synthetic compounds were evaluated for the inhibitory avidity against activities of three major isoforms of NTPDases: NTPDase-1, NTPDase-3, and NTPDase-8. Cumulatively, eighteen compounds were found to show potent inhibition (Ki = 0.0200–0.350 μM) of NTPDase-1, twelve (Ki = 0.071–1.060 μM) of NTPDase-3, and fifteen compounds inhibited (Ki = 0.0700–4.03 μM) NTPDase-8 activity. As a comparison, the Ki s of the standard inhibitor suramin were 1.260 ± 0.007, 6.39 ± 0.89 and 1.180 ± 0.002 μM, respectively. Kinetic studies were performed on lead compounds (6 , 5 , and 21) with human (h -) NTPDase-1, -3, and -8, and Lineweaver-Burk plot analysis showed that they were all competitive inhibitors. In silico study was conducted on compound 6 that showed the highest level of inhibition of NTPDase-1 to understand the binding mode in the active site of the enzyme. [ABSTRACT FROM AUTHOR]
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- 2019
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6. Synthetic nicotinic/isonicotinic thiosemicarbazides: In vitro urease inhibitory activities and molecular docking studies.
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Ali, Basharat, Mohammed Khan, Khalid, Arshia, null, Kanwal, null, Hussain, Shafqat, Hussain, Safdar, Ashraf, Muhammad, Riaz, Muhammad, Wadood, Abdul, and Perveen, Shahnaz
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NICOTINIC agonists , *CHEMICAL synthesis , *MOLECULAR docking , *STRUCTURE-activity relationships , *DRUG design - Abstract
Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3 – 27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1 H-, and 13 C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC 50 values of 1.21–51.42 μM as compared to the standard thiourea (IC 50 = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1 – 5 , 7 , 8 , 10 , 12 , 14 – 18 , 20 – 22 , 24 – 27 were found to be more active showing IC 50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study. [ABSTRACT FROM AUTHOR]
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- 2018
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7. 1-[(4′-Chlorophenyl) carbonyl-4-(aryl) thiosemicarbazide derivatives as potent urease inhibitors: Synthesis, in vitro and in silico studies.
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Ali, Basharat, Khan, Khalid Mohammed, Salar, Uzma, Kanwal, null, Hussain, Safdar, Ashraf, Muhammad, Riaz, Muhammad, Wadood, Abdul, Taha, Muhammad, and Perveen, Shahnaz
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ALDEHYDE derivatives , *CHEMICAL synthesis , *STRUCTURE-activity relationships , *MOLECULAR docking , *STATISTICAL correlation - Abstract
A series of 1-[(4′-chlorophenyl)carbonyl-4-(aryl)thiosemicarbazide derivatives 1 – 25 was synthesized and characterized by spectroscopic techniques such as EI-MS and 1 H NMR. All compounds were screened for urease inhibitory activity in vitro and demonstrated excellent inhibitory activity in the range of IC 50 = 0.32 ± 0.01–25.13 ± 0.13 μM as compared to the standard thiourea (IC 50 = 21.25 ± 0.13 μM). Amongst the potent analogs, compounds 3 (IC 50 = 2.31 ± 0.01 μM), 6 (IC 50 = 2.14 ± 0.04 μM), 10 (IC 50 = 1.14 ± 0.06 μM), 20 (IC 50 = 2.15 ± 0.05 μM), and 25 (IC 50 = 0.32 ± 0.01 μM) are many folds more active than the standard. Structure-activity relationship (SAR) was rationalized by looking at the effect of diversely substituted aryl ring on inhibitory potential which predicted that regardless of the nature of substituents, their positions on aryl ring is worth important for the potent activity. Furthermore, to verify these interpretations, in silico study was performed on all compounds and a good correlation was perceived between the biological evaluation and docking study of compounds. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies.
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Tajudeen Bale, Adebayo, Mohammed Khan, Khalid, Salar, Uzma, Chigurupati, Sridevi, Fasina, Tolulope, Ali, Farman, Kanwal, null, Wadood, Abdul, Taha, Muhammad, Sekhar Nanda, Sitanshu, Ghufran, Mehreen, and Perveen, Shahnaz
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CHALCONES , *AMYLASE inhibitors , *MOLECULAR models , *STRUCTURE-activity relationships , *NUCLEAR magnetic resonance spectroscopy - Abstract
Despite of a diverse range of biological activities associated with chalcones and bis -chalcones, they are still neglected by the medicinal chemist for their possible α -amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α -amylase inhibitors. For that purpose, a library of substituted chalcones 1 – 13 and bis -chalcones 14 – 18 were synthesized and characterized by spectroscopic techniques EI-MS and 1 H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α -amylase inhibitory activity and demonstrated good activities in the range of IC 50 = 1.25 ± 1.05–2.40 ± 0.09 µM as compared to the standard acarbose (IC 50 = 1.04 ± 0.3 µM). Limited structure–activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis -chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α -amylase enzyme, in silico studies were also conducted. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Hydrazinyl arylthiazole based pyridine scaffolds: Synthesis, structural characterization, in vitro α-glucosidase inhibitory activity, and in silico studies.
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Ali, Farman, Khan, Khalid Mohammed, Salar, Uzma, Taha, Muhammad, Ismail, Nor Hadiani, Wadood, Abdul, Riaz, Muhammad, and Perveen, Shahnaz
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PYRIDINE derivatives , *ALPHA-glucosidases , *NUCLEAR magnetic resonance , *STRUCTURE-activity relationships - Abstract
Acarbose, miglitol, and voglibose are the inhibitors of α -glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α -glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1–39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, 1 H-, and 13 C NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α -glucosidase inhibitory activity and found many folds active (IC 50 = 1.40 ± 0.01–236.10 ± 2.20 μ M) as compared to the standard acarbose having IC 50 value of 856.45 ± 5.60 μ M. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO 2 ) which have negative inductive effect were found to make important interactions with active site residues. [ABSTRACT FROM AUTHOR]
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- 2017
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10. 5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes.
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Arshad, Tanzila, Khan, Khalid Mohammed, Rasool, Najma, Salar, Uzma, Hussain, Shafqat, Asghar, Humna, Ashraf, Mohammed, Wadood, Abdul, Riaz, Muhammad, Perveen, Shahnaz, Taha, Muhammad, and Ismail, Nor Hadiani
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BENZIMIDAZOLE derivatives , *GLUCOSIDASES , *UREASE , *ANTINEOPLASTIC agents , *THIOUREA - Abstract
On the basis of previous report on promising α -glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC 50 = 8.15 ± 0.03–354.67 ± 0.19 μM) as compared to standard thiourea (IC 50 = 21.25 ± 0.15 μM). It is worth mentioning that derivatives 7 (IC 50 = 12.07 ± 0.05 μM), 8 (IC 50 = 10.57 ± 0.12 μM), 11 (IC 50 = 13.76 ± 0.02 μM), 14 (IC 50 = 15.70 ± 0.12 μM) and 22 (IC 50 = 8.15 ± 0.03 μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1 – 25 were also showed α -glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e. 2 , 7 , 8 , 11 , 14 , and 22 , in order to rationalize the binding interaction of compounds with the active site of urease enzyme. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Synthesis, in vitro β-glucuronidase inhibitory activity and in silico studies of novel (E)-4-Aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazoles.
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Salar, Uzma, Khan, Khalid Mohammed, Syed, Shazia, Ali, Farman, Ismail, Nor Hadiani, Taha, Muhammad, Perveen, Shahnaz, Wadood, Abdul, and Ghufran, Mehreen
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GLUCURONIDASE , *ISODIAZENES , *THIAZOLES , *PYRENE , *CHEMICAL synthesis - Abstract
Current research is based on the synthesis of novel ( E )-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives ( 3 – 15 ) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde ( 1 ) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate ( 2 ). While in second step, cyclization between the intermediate ( 2 ) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1 H NMR and 13 C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2 – 15 were subjected for in vitro β -glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC 50 = 3.10 ± 0.10–40.10 ± 0.90 μM and found to be even more potent than the standard d -saccharic acid 1,4-lactone (IC 50 = 48.38 ± 1.05 μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds. [ABSTRACT FROM AUTHOR]
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- 2017
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12. Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives.
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Salar, Uzma, Khan, Khalid Mohammed, Taha, Muhammad, Ismail, Nor Hadiani, Ali, Basharat, Qurat-ul-Ain, null, Perveen, Shahnaz, Ghufran, Mehreen, and Wadood, Abdul
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DRUG synthesis , *GLUCURONIDASE , *CARBOXYLATE derivatives , *AROMATIC compounds , *IN vitro studies - Abstract
Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1 H -imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26 , by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1 H -NMR and 13 C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β -glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC 50 = 1.20 ± 0.01–60.30 ± 1.40 μ M as compared to the standard d -saccharic acid 1,4-lactone (IC 50 = 48.38 ± 1.05 μ M). Compounds 1 , 3 , 4 , 6 , 9 – 19 , and 21 – 24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO 2 , F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Syntheses of new 3-thiazolyl coumarin derivatives, in vitro α-glucosidase inhibitory activity, and molecular modeling studies.
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Salar, Uzma, Taha, Muhammad, Khan, Khalid Mohammed, Ismail, Nor Hadiani, Imran, Syahrul, Perveen, Shahnaz, Gul, Sahib, and Wadood, Abdul
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COUMARIN derivatives , *GLUCOSIDASE inhibitors , *ORGANIC synthesis , *MOLECULAR models , *CHEMICAL reactions - Abstract
3-Thiazolylcoumarin derivatives 1–14 were synthesized via one-pot two step reactions, and screened for in vitro α -glucosidase inhibitory activity. All compounds showed inhibitory activity in the range of IC 50 = 0.12 ± 0.01–16.20 ± 0.23 μ M as compared to standard acarbose (IC 50 = 38.25 ± 0.12 μ M), and also found to be nontoxic. Molecular docking study was carried out in order to establish the structure-activity relationship (SAR) which demonstrated that electron rich centers at one and electron withdrawing centers at the other end of the molecules showed strong inhibitory activity. All the synthesized compounds were characterized by spectroscopic techniques such as EI-MS, HREI-MS, 1 H NMR and 13 C NMR. CHN analysis was also performed. [ABSTRACT FROM AUTHOR]
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- 2016
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14. Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of new thiazole derivatives.
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Khan, Khalid Mohammed, Qurban, Saira, Salar, Uzma, Taha, Muhammad, Hussain, Shafqat, Perveen, Shahnaz, Hameed, Abdul, Ismail, Nor Hadiani, Riaz, Muhammad, and Wadood, Abdul
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GLUCOSIDASE inhibitors , *THIAZOLE derivatives , *ORGANIC synthesis , *ACARBOSE , *MOLECULAR interactions - Abstract
Current study based on the synthesis of new thiazole derivatives via “one pot” multicomponent reaction, evaluation of their in vitro α -glucosidase inhibitory activities, and in silico studies. All synthetic compounds were fully characterized by 1 H NMR, 13 C NMR and EIMS. CHN analysis was also performed. These newly synthesized compounds showed activities in the range of IC 50 = 9.06 ± 0.10–82.50 ± 1.70 μM as compared to standard acarbose (IC 50 = 38.25 ± 0.12 μM). It is worth mentioning that most of the compounds such as 1 (IC 50 = 23.60 ± 0.39 μM), 2 (IC 50 = 22.70 ± 0.60 μM), 3 (IC 50 = 22.40 ± 0.32 μM), 4 (IC 50 = 26.5 ± 0.40 μM), 6 (IC 50 = 34.60 ± 0.60 μM), 7 (IC 50 = 26.20 ± 0.43 μM), 8 (IC 50 = 14.06 ± 0.18 μM), 9 (IC 50 = 17.60 ± 0.28 μM), 10 (IC 50 = 27.16 ± 0.41 μM), 11 (IC 50 = 19.16 ± 0.19 μM), 12 (IC 50 = 9.06 ± 0.10 μM), 13 (IC 50 = 12.80 ± 0.21 μM), 14 (IC 50 = 11.94 ± 0.18 μM), 15 (IC 50 = 16.90 ± 0.20 μM), 16 (IC 50 = 12.60 ± 0.14 μM), 17 (IC 50 = 16.30 ± 0.29 μM), and 18 (IC 50 = 32.60 ± 0.61 μM) exhibited potent inhibitory potential. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme. Newly identified α -glucosidase inhibitors except few were found to be completely non-toxic. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Benzimidazole bearing thiourea analogues: Synthesis, β-glucuronidase inhibitory potential and their molecular docking study.
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Ullah, Hayat, Zada, Hussan, Khan, Fahad, Hayat, Shawkat, Rahim, Fazal, Hussain, Amjad, Manzoor, Amina, Wadood, Abdul, Ayub, Khurshid, Rehman, Ashfaq Ur, and Sarfaraz, Sehrish
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THIOUREA , *BENZIMIDAZOLES , *MOLECULAR docking , *STRUCTURE-activity relationships , *DRUG standards - Abstract
• Synthesis of new benzimidazole bearing thiourea analogues. • In vitro screening against β -glucuronidase activity. • Identification of a new class of β -glucuronidase inhibitors. • Limited structure activity relationship was established to understand the contribution of different substituents. • In silico studies of most active compounds were performed to understand the binding interactions with enzyme. Sixteen benzimidazole-bearing thiourea analogues (1 - 16) were synthesized and tested for their β -glucuronidase inhibitory potential. All analogues showed varying degrees of activity having an IC 50 value ranging between 1.9 ± 0.1 to 29.3 ± 0.6 µM as compared to standard drug D-saccharic acid 1,4-lactone (IC 50 value = 48.1 ± 1.2 µM). Three of the compounds such as 7, 3 and 16 stand 1st, 2nd and 3rd ranked with IC 50 values 1.9 ± 0.1, 3.6 ± 0.1, 5.7 ± 0.2 µM respectively and all other analogues showed many-fold better potency as compared to standard drug. It was observed that the number, nature, position and electron donating/withdrawing effect of substituent/s on both phenyls rings greatly affect inhibitory potential. Structure-activity relationships were established and through molecular docking study binding interactions were confirmed. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2022
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16. Dihydropyrimidones: As novel class of β-glucuronidase inhibitors.
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Ali, Farman, Khan, Khalid Mohammed, Salar, Uzma, Iqbal, Sarosh, Taha, Muhammad, Ismail, Nor Hadiani, Perveen, Shahnaz, Wadood, Abdul, Ghufran, Mehreen, and Ali, Basharat
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PYRIMIDINE synthesis , *GLUCURONIDASE , *MOLECULAR docking , *STRUCTURE-activity relationships , *NUCLEAR magnetic resonance spectroscopy - Abstract
Dihydropyrimidones 1 – 37 were synthesized via a ‘one-pot’ three component reaction according to well-known Biginelli reaction by utilizing Cu(NO 3 ) 2 ·3H 2 O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC 50 = 28.16 ± .056 μM), 9 (IC 50 = 18.16 ± 0.41 μM), 10 (IC 50 = 22.14 ± 0.43 μM), 13 (IC 50 = 34.16 ± 0.65 μM), 14 (IC 50 = 17.60 ± 0.35 μM), 15 (IC 50 = 15.19 ± 0.30 μM), 16 (IC 50 = 27.16 ± 0.48 μM), 17 (IC 50 = 48.16 ± 1.06 μM), 22 (IC 50 = 40.16 ± 0.85 μM), 23 (IC 50 = 44.16 ± 0.86 μM), 24 (IC 50 = 47.16 ± 0.92 μM), 25 (IC 50 = 18.19 ± 0.34 μM), 26 (IC 50 = 33.14 ± 0.68 μM), 27 (IC 50 = 44.16 ± 0.94 μM), 28 (IC 50 = 24.16 ± 0.50 μM), 29 (IC 50 = 34.24 ± 0.47 μM), 31 (IC 50 = 14.11 ± 0.21 μM) and 32 (IC 50 = 9.38 ± 0.15 μM) found to be more potent than the standard d -saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Molecular docking study was conducted to establish the structure–activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as 1 H, 13 C NMR, EIMS and HREI-MS. [ABSTRACT FROM AUTHOR]
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- 2016
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17. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles.
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Taha, Muhammad, Ismail, Nor Hadiani, Imran, Syahrul, Wadood, Abdul, Rahim, Fazal, Saad, Syed Muhammad, Khan, Khalid Mohammed, and Nasir, Abdul
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GLUCOSIDASES , *MOLECULAR docking , *OXADIAZOLES , *CHEMICAL derivatives , *CHEMICAL synthesis , *STRUCTURE-activity relationships , *HALOGENS - Abstract
Twenty derivatives of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles ( 1 – 20 ) were synthesized and evaluated for their α -glucosidase inhibitory activities. Compounds containing hydroxyl and halogens ( 1 – 6 , and 8 – 18 ) were found to be five to seventy folds more active with IC 50 values in the range of 12.75 ± 0.10–162.05 ± 1.65 μM, in comparison with the standard drug, acarbose (IC 50 = 856.45 ± 5.60 μM). Current study explores the α -glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction. [ABSTRACT FROM AUTHOR]
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- 2016
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18. Thiadiazole derivatives as New Class of β-glucuronidase inhibitors.
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Salar, Uzma, Taha, Muhammad, Ismail, Nor Hadiani, Khan, Khalid Mohammed, Imran, Syahrul, Perveen, Shahnaz, Wadood, Abdul, and Riaz, Muhammad
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THIAZOLE derivatives , *GLUCURONIDASE , *ENZYME inhibitors , *CHEMICAL synthesis , *SINGLE step chemical reactions , *DRUG use testing , *IN vitro studies , *MOLECULAR docking - Abstract
Thiadiazole derivatives 1 – 24 were synthesized via a single step reaction and screened for in vitro β -glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC 50 = 2.16 ± 0.01–58.06 ± 1.60 μM as compare to standard d -saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure–activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N -aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques 1 H, 13 C NMR, and EIMS. [ABSTRACT FROM AUTHOR]
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- 2016
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19. Synthesis, α-glucosidase inhibitory, cytotoxicity and docking studies of 2-aryl-7-methylbenzimidazoles.
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Taha, Muhammad, Ismail, Nor Hadiani, Imran, Syahrul, Mohamad, Muhammad Helmi, Wadood, Abdul, Rahim, Fazal, Saad, Syed Muhammad, Rehman, Ashfaq ur, and Khan, Khalid Mohammed
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GLUCOSIDASE inhibitors , *CELL-mediated cytotoxicity , *CHEMICAL synthesis , *BENZIMIDAZOLES , *MOLECULAR docking , *NUCLEAR magnetic resonance spectroscopy , *CONFORMATIONAL analysis - Abstract
Benzimidazole analogs 1 – 27 were synthesized, characterized by EI-MS and 1 H NMR and their α -glucosidase inhibitory activities were found out experimentally. Compound 25 , 19 , 10 and 20 have best inhibitory activities with IC 50 values 5.30 ± 0.10, 16.10 ± 0.10, 25.36 ± 0.14 and 29.75 ± 0.19 respectively against α -glucosidase. Compound 6 and 12 has no inhibitory activity against α -glucosidase enzyme among the series. Further studies showed that the compounds are not showing any cytotoxicity effect. The docking studies of the compounds as well as the experimental activities of the compounds correlated well. From the molecular docking studies, it was observed that the top ranked conformation of all the compounds fit well in the active site of the homology model of α -glucosidase. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
20. Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions.
- Author
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Taha, Muhammad, Ismail, Nor Hadiani, Javaid, Kulsoom, Imran, Syahrul, Anouar, El Hassane, Wadood, Abdul, Atia-tul-Wahab, null, Ali, Muhammad, Khan, Khalid Mohammed, Saad, Syed Muhammad, Rahim, Fazal, and Choudhary, M. Iqbal
- Subjects
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GLUCOSIDASE inhibitors , *ANTIMETABOLITES , *ISOMERISM , *ENZYMES , *VIBRATION (Mechanics) - Abstract
2-Indolcarbohydrazones 1 – 28 were synthesized and evaluated for their α -glucosidase inhibitory potential. A varying degree of inhibitory potential with IC 50 values in the range of 2.3 ± 0.11–226.4 ± 6.8 μM was observed while comparing these outcomes with the standard acarbose (IC 50 = 906.0 ± 6.3 μM). The stereochemistry of ten ( 10 ) randomly selected compounds ( 1 , 3 , 6 , 8 , 12 , 18 , 19 , 23 , 25 and 28 ) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of ν C O , ν N C and ν CH (CH in N CH -R). It was observed that except compound 18 , all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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21. Synthesis, in-vitro and in-silico studies of triazinoindole bearing bis-Schiff base as β-glucuronidase inhibitors.
- Author
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Ullah, Hayat, Ahmad, Shakeel, Khan, Fahad, Taha, Muhammad, Rahim, Fazal, Sarfraz, Maliha, Aziz, Aamir, and Wadood, Abdul
- Subjects
- *
STRUCTURE-activity relationships , *MOLECULAR docking , *MOLECULAR interactions - Abstract
• Synthesis of new triazinoindole bearing bis -Schiff base derivatives and fully characterized by various spectroscopic techniques. • In vitro screening against β -glucuronidase inhibitors. • Identification of a new class of β -glucuronidase inhibitors. • Structure activity relationship was established to understand the contribution of different substituents. • In silico studies of most active compounds were performed to understand the binding interactions with enzyme. Triazinoindole bearing bis -Schiff base analogs (1–20) were synthesized by triazinoindole-thione ring formation, triazinoindole-thiol-phenylethanone, followed by triazinoindole bis -Schiff base formation. Synthesized analogs showed β -glucuronidase potential with IC 50 value ranging between 2.60 ± 0.10 to 55.40 ± 1.60 µ M as compared to standard d -saccharic acid 1,4-lactone (IC 50 = 48.10 ± 1.2 µ M). Analog 20 was the most potent one with IC 50 value 2.60 ± 0.10 µ M. Analogs 17, 4 showed IC 50 values 5.20 ± 0.20 and 5.70 ± 0.20 µ M respectively and withstand 2nd and 3rd ranked scaffolds among the synthesized analogs. All other sixteen analogs showed many-fold better potency with IC 50 values ranging from 7.9 ± 0.2 to 48.1 ± 1.2 µ M. The structure-activity relationship was established and confirmed of binding interactions through molecular docking studies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
22. Synthesis and screening of (E)-3-(2-benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazine analogs as novel dual inhibitors of α-amylase and α-glucosidase.
- Author
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Shamim, Shahbaz, Khan, Khalid Mohammed, Ullah, Nisar, Chigurupati, Sridevi, Wadood, Abdul, Ur Rehman, Ashfaq, Ali, Muhammad, Salar, Uzma, Alhowail, Ahmad, Taha, Muhammad, and Perveen, Shahnaz
- Subjects
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AMYLASES , *GLUCOSIDASES , *STRUCTURE-activity relationships , *PROTEIN-ligand interactions , *MOLECULAR docking , *ACARBOSE , *CHEMICAL inhibitors - Abstract
• (E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines 1–27 were synthesized. • In vitro α -amylase and α -glucosidase inhibitory activities were performed. • Structure-activity relationship was rationalized. • Kinetic studies was carried out. • In silico studies were also carried out. (E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1 – 27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α -amylase and α -glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14 – 17 , 19 , and 21 – 25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC 50 values ranging (IC 50 = 13.02 ± 0.04–46.90 ± 0.05 µM) and (IC 50 = 13.09 ± 0.08–46.44 ± 0.24 µM) in comparison to standard acarbose (IC 50 = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α -amylase and α -glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α -amylase and α -glucosidase inhibitors 5 , 7 , 9 , 15 , 24 , and 27 , suggested non-competitive and competitive types of inhibition mechanism for α -amylase and α -glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H-<, < - <, and <-H etc., against the corresponding targets. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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