Displaying publications 1 - 20 of 94 in total

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  1. Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, et al.
    Bioorg Chem, 2016 Feb;64:29-36.
    PMID: 26637946 DOI: 10.1016/j.bioorg.2015.11.006
    Newly synthesized benzimidazole hydrazone derivatives 1-26 were evaluated for their α-glucosidase inhibitory activity. Compounds 1-26 exhibited varying degrees of yeast α-glucosidase inhibitory activity with IC50 values between 8.40 ± 0.76 and 179.71 ± 1.11 μM when compared with standard acarbose. In this assay, seven compounds that showed highest inhibitory effects than the rest of benzimidazole series were identified. All the synthesized compounds were characterized by different spectroscopic methods adequately. We further evaluated the interaction of the active compounds with enzyme with the help of docking studies.
  2. Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F, et al.
    Bioorg Chem, 2015 Dec;63:36-44.
    PMID: 26432614 DOI: 10.1016/j.bioorg.2015.09.004
    Biscoumarin analogs 1-18 have been synthesized, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All compounds showed variety of α-glucosidase inhibitory potential ranging in between 13.5±0.39 and 104.62±0.3μM when compared with standard acarbose having IC50 value 774.5±1.94μM. The binding interactions of the most active analogs were confirmed through molecular docking. The compounds showed very good interactions with enzyme. All synthesized compounds 1-18 are new. Our synthesized compounds can further be studied to developed lead compounds.
  3. Zawawi NK, Taha M, Ahmat N, Wadood A, Ismail NH, Rahim F, et al.
    Bioorg Med Chem, 2015 Jul 1;23(13):3119-25.
    PMID: 26001340 DOI: 10.1016/j.bmc.2015.04.081
    A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone (3a-3r) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a-3d, 3e-3j, 3l-3o, 3q and 3r showed excellent inhibitory potentials much better than the standard (IC50=48.4±1.25μM: d-saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies.
  4. Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F
    Bioorg Chem, 2017 02;70:184-191.
    PMID: 28043716 DOI: 10.1016/j.bioorg.2016.12.009
    Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
  5. Zaman K, Rahim F, Taha M, Wadood A, Shah SAA, Ahmed QU, et al.
    Sci Rep, 2019 11 05;9(1):16015.
    PMID: 31690793 DOI: 10.1038/s41598-019-52100-0
    Here in this study regarding the over expression of TP, which causes some physical, mental and socio problems like psoriasis, chronic inflammatory disease, tumor angiogenesis and rheumatoid arthritis etc. By this consideration, the inhibition of this enzyme is vital to secure life from serious threats. In connection with this, we have synthesized twenty derivatives of isoquinoline bearing oxadiazole (1-20), characterized through different spectroscopic techniques such as HREI-MS, 1H- NMR and 13C-NMR and evaluated for thymidine phosphorylase inhibition. All analogues showed outstanding inhibitory potential ranging in between 1.10 ± 0.05 to 54.60 ± 1.50 µM. 7-Deazaxanthine (IC50 = 38.68 ± 1.12 µM) was used as a positive control. Through limited structure activity relationships study, it has been observed that the difference in inhibitory activities of screened analogs are mainly affected by different substitutions on phenyl ring. The effective binding interactions of the most active analogs were confirmed through docking study.
  6. Zaman K, Rahim F, Taha M, Ullah H, Wadood A, Nawaz M, et al.
    Bioorg Chem, 2019 08;89:103024.
    PMID: 31176853 DOI: 10.1016/j.bioorg.2019.103024
    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the urease inhibitory potential. For that purpose, benzimidazole analogues 1-19 were synthesized and screened for in vitro urease inhibitory potential. Structures of all synthetic analogues were deduced by different spectroscopic techniques. All analogues revealed inhibition potential with IC50 values of 0.90 ± 0.01 to 35.20 ± 1.10 μM, when compared with the standard thiourea (IC50 = 21.40 ± 0.21 μM). Limited SAR suggested that the variations in the inhibitory potentials of the analogues are the result of different substitutions on phenyl ring. In order to rationalize the binding interactions of most active compounds with the active site of urease enzyme, molecular docking study was conducted.
  7. Zaman K, Rahim F, Taha M, Wadood A, Adnan Ali Shah S, Gollapalli M, et al.
    Bioorg Chem, 2019 08;89:102999.
    PMID: 31151055 DOI: 10.1016/j.bioorg.2019.102999
    Isoquinoline analogues (KA-1 to 16) have been synthesized and evaluated for their E. coli thymidine phosphorylase inhibitory activity. Except compound 11, all other analogs showed outstanding thymidine inhibitory potential ranging in between 4.40 ± 0.20 to 69.30 ± 1.80 µM when compared with standard drug 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). Structure Activity Relationships has been established for all compounds, mainly based on substitution pattern on phenyl ring. All analogs were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and EI-MS. The binding interactions of isoquinoline analogues with the active site of TP enzyme, the molecular docking studies were performed. Furthermore, the angiogenic inhibitory potentials of isoquinoline analogues (KA-1-9, 14, 12 and 16) were determined in the presence of standard drug Dexamethasone based on percentage inhibitions at various concentrations. Herein this work analogue KA-12, 14 and 16 emerged with most potent angiogenic inhibitory potentials among the synthesized analogues.
  8. Zaman K, Rahim F, Taha M, Sajid M, Hayat S, Nawaz M, et al.
    Bioorg Chem, 2021 10;115:105199.
    PMID: 34329995 DOI: 10.1016/j.bioorg.2021.105199
    Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC50 = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC50 = 0.60 ± 0.01 to 24.10 ± 0.70 µM) which displayed that it is most potent class of urease inhibitor. Analog 1-9, and 11-13 emerged with many times greater antiurease potential than thiourea, in which analog 1, 2, 3, 4, 8, 9, and 11 (IC50 = 3.50 ± 0.10, 7.20 ± 0.20, 1.30 ± 0.10, 2.30 ± 0.10, 0.60 ± 0.01, 1.05 ± 0.10 and 2.60 ± 0.10 µM respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1, 3, 4, 8, and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3, 8, and 9 were found with minimum cytotoxic outline at higher concentration (500 µg/mL). All analogs were characterized through 1H NMR, 13C NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.
  9. Yary T, Soleimannejad K, Abd Rahim F, Kandiah M, Aazami S, Poor SJ, et al.
    Lipids Health Dis, 2010;9:133.
    PMID: 21087475 DOI: 10.1186/1476-511X-9-133
    BACKGROUND: Despite significant improvements in the treatment of coronary heart disease (CHD), it is still a major cause of mortality and morbidity among the Iranian population. Epidemiological studies have documented that risk factors including smoking and the biochemical profile are responsible for the development of acute myocardial infarction (AMI). Psychological factors have been discussed as potential risk factors for coronary heart disease. Among emotional factors, depression correlates with coronary heart disease, particularly myocardial infarction.
    METHODS: This case-control study was conducted on 120 cases (69 males and 51 females) of acute myocardial infarction (AMI) and 120 controls, with a mean age of 62.48 ± 15.39 years. Cases and controls were matched by age, residence and sex.
    RESULTS: The results revealed that severe depression was independently associated with the risk of AMI (P = 0.025, OR = 2.6, 95% CI 1.1-5.8). The analysis of variables indicated that risk factors for developing depression were unmarried, low levels of polyunsaturated fatty acids (PUFAs), total dietary fiber (TDF) and carbohydrates. The levels of these dietary factors were lowest in severely depressed patients compared to those categorised as moderate or mild cases. Furthermore, severely depressed subjects were associated with higher levels of total cholesterol, high systolic blood pressure (SBP) and WHR. Age, income, a family history of coronary heart disease, education level, sex, employment and smoking were not associated with severe depression.
    CONCLUSION: The present study demonstrated that severe depression symptoms are independent risk factors for AMI. Furthermore, severe depression was associated with an unhealthy diet and AMI risk factors.
    Study site: Mostafa Hospital, Ilam Province, Iran
  10. Ullah H, Rahim F, Taha M, Uddin I, Wadood A, Shah SAA, et al.
    Bioorg Chem, 2018 08;78:58-67.
    PMID: 29533215 DOI: 10.1016/j.bioorg.2018.02.020
    We have synthesized oxadiazole derivatives (1-16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ± 0.05 to 49.60 ± 1.30 μM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ± 1.12 μM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.
  11. Taha M, Ismail NH, Jamil W, Rashwan H, Kashif SM, Sain AA, et al.
    Eur J Med Chem, 2014 Sep 12;84:731-8.
    PMID: 25069019 DOI: 10.1016/j.ejmech.2014.07.078
    4-Methylbenzimidazole 1-28 novel derivatives were synthesized and evaluated for their antiglycation and antioxidant activities. Compounds 1-7 and 11 showed excellent activities ranged 140-280 μM, better than standard drug rutin (294.46 ± 1.50 μM). Compound 1-28 were also evaluated for DPPH activities. Compounds 1-8 showed excellent activities, ranging 12-29 μM, better than standard drug n-propylgallate (IC50 = 30.30 ± 0.40 μM). For superoxide anion scavenging activity, compounds 1-7 showed better activity than standard n-propylgallate (IC50 = 106.34 ± 1.6 μM), ranged 82-104 μM. These compounds were found to be nontoxic to THP-1 cells.
  12. Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Riaz M
    Bioorg Med Chem, 2015 Nov 15;23(22):7211-8.
    PMID: 26507431 DOI: 10.1016/j.bmc.2015.10.017
    Disulfide analogs (1-20) have been synthesized, characterized by HR-MS, (1)H NMR and (13)C NMR and screened for urease inhibitory potential. All compounds were found to have varied degree of urease inhibitory potential ranging in between 0.4 ± 0.01 and 18.60 ± 1.24 μM when compared with standard inhibitor thiourea with IC50 19.46 ± 1.20 μM. Structure activity relationship has been established. The binding interactions of compounds with enzyme were confirmed through molecular docking. All the synthesized compounds 1-20 are new. Our compounds are cheaply synthesizable with high yield and can further be studied to discovery lead compounds. We further, tested for carbonic anhydrase, PDE1 and butyrylcholinesterase but they show no activity. On the other hand we evaluated all compounds for cytotoxicity they showed no toxicity.
  13. Taha M, Ismail NH, Javaid K, Imran S, Anouar el H, Wadood A, et al.
    Bioorg Chem, 2015 Dec;63:24-35.
    PMID: 26398141 DOI: 10.1016/j.bioorg.2015.09.001
    2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). 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 νCO, νNC and νCH (CH in NCH-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.
  14. Taha M, Ismail NH, Imran S, Selvaraj M, Rahim A, Ali M, et al.
    Bioorg Med Chem, 2015 Dec 1;23(23):7394-404.
    PMID: 26526743 DOI: 10.1016/j.bmc.2015.10.037
    A series of compounds consisting of 25 novel oxadiazole-benzohydrazone hybrids (6-30) were synthesized through a five-step reaction sequence and evaluated for their β-glucuronidase inhibitory potential. The IC50 values of compounds 6-30 were found to be in the range of 7.14-44.16μM. Compounds 6, 7, 8, 9, 11, 13, 18, and 25 were found to be more potent than d-saccharic acid 1,4-lactone (48.4±1.25μM). These compounds were further subjected for molecular docking studies to confirm the binding mode towards human β-d-glucuronidase active site. Docking study for compound 13 (IC50=7.14±0.30μM) revealed that it adopts a binding mode that fits within the entire pocket of the binding site of β-d-glucuronidase. Compound 13 has the maximum number of hydrogens bonded to the residues of the active site as compared to the other compounds, that is, the ortho-hydroxyl group forms hydrogen bond with carboxyl side chain of Asp207 (2.1Å) and with hydroxyl group of Tyr508 (2.6Å). The other hydroxyl group forms hydrogen bond with His385 side chain (2.8Å), side chain carboxyl oxygen of Glu540 (2.2Å) and Asn450 side-chain's carboxamide NH (2.1Å).
  15. Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Khan KM, et al.
    Bioorg Chem, 2016 Jun;66:80-7.
    PMID: 27038849 DOI: 10.1016/j.bioorg.2016.03.010
    Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and (1)H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4±0.10 to 34.43±2.10μM when compared with standard thiourea (IC50 19.46±1.20μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1-18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking.
  16. Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Saad SM, et al.
    Bioorg Chem, 2016 Jun;66:117-23.
    PMID: 27149363 DOI: 10.1016/j.bioorg.2016.04.006
    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 IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). 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.
  17. Taha M, Sultan S, Nuzar HA, Rahim F, Imran S, Ismail NH, et al.
    Bioorg Med Chem, 2016 08 15;24(16):3696-704.
    PMID: 27312423 DOI: 10.1016/j.bmc.2016.06.008
    Thirty N-arylidenequinoline-3-carbohydrazides (1-30) have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty four analogs showed outstanding β-glucuronidase activity having IC50 values ranging between 2.11±0.05 and 46.14±0.95 than standard d-saccharic acid 1,4 lactone (IC50=48.4±1.25μM). Six analogs showed good β-glucuronidase activity having IC50 values ranging between 49.38±0.90 and 80.10±1.80. Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. Our study identifies novel series of potent β-glucuronidase inhibitors for further investigation.
  18. Taha M, Ismail NH, Imran S, Mohamad MH, Wadood A, Rahim F, et al.
    Bioorg Chem, 2016 Apr;65:100-9.
    PMID: 26894559 DOI: 10.1016/j.bioorg.2016.02.004
    Benzimidazole analogs 1-27 were synthesized, characterized by EI-MS and (1)HNMR and their α-glucosidase inhibitory activities were found out experimentally. Compound 25, 19, 10 and 20 have best inhibitory activities with IC50 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.
  19. Taha M, Ismail NH, Imran S, Rashwan H, Jamil W, Ali S, et al.
    Bioorg Chem, 2016 Apr;65:48-56.
    PMID: 26855413 DOI: 10.1016/j.bioorg.2016.01.007
    6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and β-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10±2.50μM) and 4 (IC50=240.30±2.90μM) was found to be most active compound of this series, while compounds 3 (IC50=260.10±2.50μM), 6 (IC50=290.60±3.60μM), 13 (IC50=288.20±3.00μM) and 26 (IC50=292.10±3.20μM) also showed better activities than the standard rutin (IC50=294.50±1.50μM). In antioxidant assay, compound 1 (IC50=69.45±0.25μM), 2 (IC50=58.10±2.50μM), 3 (IC50=74.25±1.10μM), and 4 (IC50=72.50±3.30μM) showed good activities. In β-glucuronidase activity, compounds 3 (IC50=29.25±0.50μM), compound 1 (IC50=30.10±0.60μM) and compound 4 (IC50=46.10±1.10μM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50±1.25μM) and their interaction with the enzyme was confirm by docking studies.
  20. Taha M, Ismail NH, Imran S, Selvaraj M, Rashwan H, Farhanah FU, et al.
    Bioorg Chem, 2015 Aug;61:36-44.
    PMID: 26073618 DOI: 10.1016/j.bioorg.2015.05.010
    Twenty five 4, 6-dichlorobenzimidazole derivatives (1-25) have been synthesized and evaluated against β-glucuronidase inhibitory activity. The compounds which actively inhibit β-glucuronidase activity have IC50 values ranging between 4.48 and 46.12 μM and showing better than standard d-saccharic acid 1,4 lactone (IC50=48.4 ± 1.25 μM). Molecular docking provided potential clues to identify interactions between the active molecules and the enzyme which further led us to identify plausible binding mode of all the benzimidazole derivatives. This study confirmed that presence of hydrophilic moieties is crucial to inhibit the human β-glucuronidase.
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