Displaying publications 1 - 20 of 36 in total

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  1. Saddique FA, Aslam S, Ahmad M, Ashfaq UA, Muddassar M, Sultan S, et al.
    Molecules, 2021 May 20;26(10).
    PMID: 34065194 DOI: 10.3390/molecules26103043
    Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis*
  2. Leong SW, Abas F, Lam KW, Yusoff K
    Bioorg Med Chem Lett, 2018 02 01;28(3):302-309.
    PMID: 29292226 DOI: 10.1016/j.bmcl.2017.12.048
    A series of thirty-four diarylpentanoids derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity. Eleven compounds (19, 20, 21, 24, 27, 28, 29, 31, 32, 33 and 34) were found to significantly inhibit α-glucosidase in which compounds 28, 31 and 32 demonstrated the highest activity with IC50 values ranging from 14.1 to 15.1 µM. Structure-activity comparison shows that multiple hydroxy groups are essential for α-glucosidase inhibitory activity. Meanwhile, 3,4-dihydroxyphenyl and furanyl moieties were found to be crucial in improving α-glucosidase inhibition. Molecular docking analyses further confirmed the critical role of both 3,4-dihydroxyphenyl and furanyl moieties as they bound to α-glucosidase active site in different mode. Overall result suggests that diarylpentanoids with both five membered heterocyclic ring and polyhydroxyphenyl moiety could be a new lead design in the search of novel α-glucosidase inhibitor.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  3. Barakat A, Islam MS, Al-Majid AM, Ghabbour HA, Fun HK, Javed K, et al.
    Bioorg Med Chem, 2015 Oct 15;23(20):6740-8.
    PMID: 26381063 DOI: 10.1016/j.bmc.2015.09.001
    We describe here the synthesis of dihydropyrimidines derivatives 3a-p, and evaluation of their α-glucosidase enzyme inhibition activities. Compounds 3b (IC50=62.4±1.5 μM), 3c (IC50=25.3±1.26 μM), 3d (IC50=12.4±0.15 μM), 3e (IC50=22.9±0.25 μM), 3g (IC50=23.8±0.17 μM), 3h (IC50=163.3±5.1 μM), 3i (IC50=30.6±0.6 μM), 3m (IC50=26.4±0.34 μM), and 3o (IC50=136.1±6.63 μM) were found to be potent α-glucosidase inhibitors in comparison to the standard drug acarbose (IC50=840±1.73 μM). The compounds were also evaluated for their in vitro cytotoxic activity against PC-3, HeLa, and MCF-3 cancer cell lines, and 3T3 mouse fibroblast cell line. All compounds were found to be non cytotoxic, except compounds 3f and 3m (IC50=17.79±0.66-20.44±0.30 μM), which showed a weak cytotoxic activity against the HeLa, and 3T3 cell lines. In molecular docking simulation study, all the compounds were docked into the active site of the predicted homology model of α-glucosidase enzyme. From the docking result, it was observed that most of the synthesized compounds showed interaction through carbonyl oxygen atom and polar phenyl ring with active site residues of the enzyme.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  4. Khan KM, Qurban S, Salar U, Taha M, Hussain S, Perveen S, et al.
    Bioorg Chem, 2016 10;68:245-58.
    PMID: 27592296 DOI: 10.1016/j.bioorg.2016.08.010
    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 IC50=9.06±0.10-82.50±1.70μM as compared to standard acarbose (IC50=38.25±0.12μM). It is worth mentioning that most of the compounds such as 1 (IC50=23.60±0.39μM), 2 (IC50=22.70±0.60μM), 3 (IC50=22.40±0.32μM), 4 (IC50=26.5±0.40μM), 6 (IC50=34.60±0.60μM), 7 (IC50=26.20±0.43μM), 8 (IC50=14.06±0.18μM), 9 (IC50=17.60±0.28μM), 10 (IC50=27.16±0.41μM), 11 (IC50=19.16±0.19μM), 12 (IC50=9.06±0.10μM), 13 (IC50=12.80±0.21μM), 14 (IC50=11.94±0.18μM), 15 (IC50=16.90±0.20μM), 16 (IC50=12.60±0.14μM), 17 (IC50=16.30±0.29μM), and 18 (IC50=32.60±0.61μM) 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.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  5. Salar U, Taha M, Khan KM, Ismail NH, Imran S, Perveen S, et al.
    Eur J Med Chem, 2016 Oct 21;122:196-204.
    PMID: 27371923 DOI: 10.1016/j.ejmech.2016.06.037
    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 IC50 = 0.12 ± 0.01-16.20 ± 0.23 μM as compared to standard acarbose (IC50 = 38.25 ± 0.12 μM), 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.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis*
  6. Yeye EO, Kanwal, Mohammed Khan K, Chigurupati S, Wadood A, Ur Rehman A, et al.
    Bioorg Med Chem, 2020 06 01;28(11):115467.
    PMID: 32327353 DOI: 10.1016/j.bmc.2020.115467
    Thirty-three 4-amino-1,2,4-triazole derivatives 1-33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via1H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1-33 exhibited good to moderate in vitro α-amylase and α-glucosidase inhibitory activities in the range of IC50 values 2.01 ± 0.03-6.44 ± 0.16 and 2.09 ± 0.08-6.54 ± 0.10 µM as compared to the standard acarbose (IC50 = 1.92 ± 0.17 µM) and (IC50 = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1-33 followed mixed and non-competitive type of inhibitions against α-amylase and α-glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  7. Rahim F, Tariq S, Taha M, Ullah H, Zaman K, Uddin I, et al.
    Bioorg Chem, 2019 11;92:103284.
    PMID: 31546207 DOI: 10.1016/j.bioorg.2019.103284
    New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  8. Tariq QU, Malik S, Khan A, Naseer MM, Khan SU, Ashraf A, et al.
    Bioorg Chem, 2019 03;84:372-383.
    PMID: 30530108 DOI: 10.1016/j.bioorg.2018.11.053
    Xanthenone based hydrazone derivatives (5a-n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a-n) are characterized by their FTIR, 1H NMR, 13C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC50 = 375.38 ± 0.12 µM). Amongst the series, compound 5l (IC50 = 62.25 ± 0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis*
  9. Abbasi MA, Hassan M, Ur-Rehman A, Siddiqui SZ, Hussain G, Shah SAA, et al.
    Comput Biol Chem, 2018 Dec;77:72-86.
    PMID: 30245349 DOI: 10.1016/j.compbiolchem.2018.09.007
    The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (1; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound 1 with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) in a basic, polar and protic medium to obtain the parent sulfonamide 3 which was then treated with different electrophiles, 4a-g, in a polar and aprotic medium to acquire the designed molecules, 5a-g. These convergent derivatives were evaluated for their inhibitory potential against α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Acarbose was used as a reference standard for α-glucosidase inhibition while eserine for AChE and BChE inhibition. Some of the synthesized compounds were identified as promising inhibitors of these three enzymes and their bioactivity potentials were also supported by molecular docking study. The most active compounds among the synthetic analogues might be helpful in drug discovery and development for the treatment of type 2 diabetes and Alzhiemer's diseases.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  10. 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.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  11. Saleem F, Kanwal, Khan KM, Chigurupati S, Solangi M, Nemala AR, et al.
    Bioorg Chem, 2021 01;106:104489.
    PMID: 33272713 DOI: 10.1016/j.bioorg.2020.104489
    Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  12. Ali F, Khan KM, Salar U, Taha M, Ismail NH, Wadood A, et al.
    Eur J Med Chem, 2017 Sep 29;138:255-272.
    PMID: 28672278 DOI: 10.1016/j.ejmech.2017.06.041
    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 (IC50 = 1.40 ± 0.01-236.10 ± 2.20 μM) as compared to the standard acarbose having IC50 value of 856.45 ± 5.60 μM. 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 (NO2) which have negative inductive effect were found to make important interactions with active site residues.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  13. Adegboye AA, Khan KM, Salar U, Aboaba SA, Kanwal, Chigurupati S, et al.
    Eur J Med Chem, 2018 Apr 25;150:248-260.
    PMID: 29533872 DOI: 10.1016/j.ejmech.2018.03.011
    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC50 = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  14. 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.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  15. Hassan LR, Anouar EH, Bahron H, Abdullah F, Mohd Tajuddin A
    J Biol Inorg Chem, 2020 03;25(2):239-252.
    PMID: 31974764 DOI: 10.1007/s00775-020-01755-6
    Hydroxamic acids [R(CO)N(OH)R'] are flexible compounds for organic and inorganic analyses due to their frailer structures compared to the carboxylic acid. The syntheses and characterization of benzohydroxamic acid (BHA), its CH3-, OCH3-, Cl- para-substituted derivatives and their Cr(III) complexes are reported herein. The metal complexes were synthesized by reacting the hydroxamic acids with chromium(III) chloride hexahydrate in 2:1 molar ratio. The compounds were characterized via melting point, elemental analysis, FTIR, 1H and 13C NMR, TGA, mass spectrometry, molar conductance and UV-Visible. Data analysis suggests that each complex has the Cr(III) center coordinated to the carbonyl and hydroxy oxygen atoms of the hydroxamic acids in bidentate O,O manner and two water molecules to form octahedral geometry. Non-electrolytic behavior of the complexes was shown through their low molar conductivity. Cytotoxicity study against HCT116 and alpha-glucosidase inhibition test revealed that all complexes have higher activity than their parent ligands. Molecular docking study shows that the docking of active complexes is thermodynamically favorable and the inhibition efficiency may depend on the types and the numbers of molecular interactions established in the corresponding stable conformers.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  16. Taha M, Imran S, Salahuddin M, Iqbal N, Rahim F, Uddin N, et al.
    Bioorg Chem, 2021 05;110:104808.
    PMID: 33756236 DOI: 10.1016/j.bioorg.2021.104808
    We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1-17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC50 values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC50 = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC50 value 1.60 μM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1-15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through 1H, 13CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  17. Ishaq M, Taslimi P, Shafiq Z, Khan S, Ekhteiari Salmas R, Zangeneh MM, et al.
    Bioorg Chem, 2020 07;100:103924.
    PMID: 32442818 DOI: 10.1016/j.bioorg.2020.103924
    In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  18. Abdullah MA, Lee YR, Mastuki SN, Leong SW, Wan Ibrahim WN, Mohammad Latif MA, et al.
    Bioorg Chem, 2020 11;104:104277.
    PMID: 32971414 DOI: 10.1016/j.bioorg.2020.104277
    A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  19. Rahim F, Ullah K, Ullah H, Wadood A, Taha M, Ur Rehman A, et al.
    Bioorg Chem, 2015 Feb;58:81-7.
    PMID: 25528720 DOI: 10.1016/j.bioorg.2014.12.001
    A new series of triazinoindole analogs 1-11 were synthesized, characterized by EI-MS and (1)H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC50 value ranging between 2.46±0.008 and 312.79±0.06 μM when compared with the standard acarbose (IC50, 38.25±0.12 μM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC50 values 2.46±0.008, 37.78±0.05, 28.91±0.0, 38.12±0.04, 37.43±0.03, 36.89±0.06 and 37.11±0.05 μM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis
  20. Taha M, Ismail NH, Imran S, Rokei MQB, Saad SM, Khan KM
    Bioorg Med Chem, 2015 Aug 01;23(15):4155-4162.
    PMID: 26183542 DOI: 10.1016/j.bmc.2015.06.060
    Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC50 values were being compared to the standard acarbose (IC50=856.45 ± 5.60 μM) and it was found that compounds 6-9, 12, 13, 16, 18, 20, 22-28 were found to be more active than acarbose, while other compounds showed no activity. Structure-activity relationship (SAR) studies suggest that oxadiazole benzohydrazones (6-28) inhibitory potential is dependent on substitution of the N-benzylidene part. Compound 18 (IC50=2.64 ± 0.05 μM), which has trihydroxy substitution at C-2', C-4', and C-5' on N-benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC50=856.45 ± 5.60 μM). Compound 23 (IC50=34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2' to C-4' (6) and C-3' (7) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16, 28, and 27) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential.
    Matched MeSH terms: Glycoside Hydrolase Inhibitors/chemical synthesis*
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