Displaying publications 1 - 20 of 797 in total

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  1. Muhammad MT, Beniddir MA, Phongphane L, Abu Bakar MH, Hussin MH, Awang K, et al.
    Fitoterapia, 2024 Apr;174:105873.
    PMID: 38417682 DOI: 10.1016/j.fitote.2024.105873
    Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ14-17-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ16, 17-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC50) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 μM, respectively compared with the reference acarbose (IC50 = 34.4 ± 0.1 μM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.
    Matched MeSH terms: Molecular Structure
  2. Ngadni MA, Chong SL, Kamarudin MNA, Hazni H, Litaudon M, Supratman U, et al.
    Fitoterapia, 2024 Mar;173:105765.
    PMID: 38042506 DOI: 10.1016/j.fitote.2023.105765
    A phytochemical study on the bark of Chisocheton erythrocarpus Hiern (Meliaceae) has led to the isolation of six new phragmalin-type limonoids named erythrocarpines I - N (1-6) along with one known limonoid, erythrocarpine F (7). Their structures were fully characterized by spectroscopic methods. The pre-treatment of NG108-15 cells with 1-5, 7 (2 h) demonstrated low to good protective effects against H2O2 exposure; 1 (83.77% ± 1.84 at 12.5 μM), 2 (69.07 ± 2.01 at 12.5 μM), 3 (80.38 ± 2.1 at 12.5 μM), 4 (62.33 ± 1.95 at 25 μM),5 (58.67 ± 1.85 at 50 μM) and 7 (66.07 ± 2.03 at 12.5 μM). Interestingly, 1 and 3 demonstrated comparable protective effects to positive control epigallocatechin gallate (EGCG) with similar cell viability capacity (≈ 80%), having achieved that at lower concentration (12.5 μM) than EGCG (50 μM). Collectively, the results suggested the promising use of 1 and 3 as potential neuroprotective agents against hydrogen peroxide-induced cytotoxicity in neuronal model.
    Matched MeSH terms: Molecular Structure
  3. Zailan AAD, Karunakaran T, Santhanam R, Suriaty Yaakop A, Mohan S, Abu Bakar MH, et al.
    Chem Biodivers, 2024 Mar;21(3):e202301936.
    PMID: 38268343 DOI: 10.1002/cbdv.202301936
    The genus Calophyllum from the family Calophyllaceae has been extensively investigated in the past due to its rich source of bioactive phenolics such as coumarins, chromanones, and xanthones. In this study, phytochemical investigation on the stem bark of Calophyllum havilandii has afforded a new 4-propyldihydrocoumarin derivative, havilarin (1) together with calolongic acid (2), caloteysmannic acid (3), isocalolongic acid (4), euxanthone (5), and β-sitosterol (6). The chemical structure of compound 1 was elucidated and established based on detailed spectroscopic techniques, including MS, IR, UV, 1D and 2D NMR. The results of anti-bacillus study indicated that the chloroform extract showed promising activities with MIC value ranging between 0.5 to 1 μg/mL on selected bacillus strains. Besides, the plant extracts and compounds 1-4 were assessed for their cytotoxicity potential on HL-7702 cell line. All the tested plant extracts and respective chemical constituents displayed non-cytotoxic activity on HL-7702 cell line.
    Matched MeSH terms: Molecular Structure
  4. Tan YS, Ng MP, Tan CH, Tang WK, Sim KS, Yong KT, et al.
    J Nat Prod, 2024 Feb 23;87(2):286-296.
    PMID: 38284153 DOI: 10.1021/acs.jnatprod.3c00960
    Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 μM, respectively.
    Matched MeSH terms: Molecular Structure
  5. Ariffin NHM, Hasham R, Hamzah MAAM, Park CS
    Fitoterapia, 2024 Jan;172:105755.
    PMID: 38000761 DOI: 10.1016/j.fitote.2023.105755
    Ficus deltoidea was known for its potent antioxidant, anti-melanogenic and photoprotective skin barrier activities. These properties are contributed by its biomarkers which are vitexin and isovitexin. This study aims to optimize the yield of methanolic extraction of Ficus deltoidea leaves (EFD) and evaluate their effects on skin barrier function and hydration. For optimization, Box-Behnken design was utilized to investigate the effects of methanol concentration, sonication time, and solvent-to-sample ratio on the yields of vitexin and isovitexin in EFD. The optimal yields obtained were 32.29 mg/g for vitexin and 35.87 mg/g for isovitexin. The optimum extraction conditions were 77.66% methanol concentration, 20.03 min sonication time, and 19.88 mL/g solvent-to-sample ratio. The quantitative real-time polymerase chain reaction was utilized to measure variant marker genes of transglutaminase-1, caspase 14, ceramide synthase 3, involucrin, and filaggrin of EFD-induced keratinocyte differentiation by in vitro study. Exposure to EFD has elevated the mRNA levels of all tested marker genes by 0.7-9.2 folds. Then, in vivo efficacy study was conducted on 20 female subjects for 14 days to evaluate skin biophysical assessment of hydration. EFD topical formulation treatment successfully increased skin hydration on day 7 (43.74%) and day 14 (47.23%). In silico study by molecular docking was performed to identify intermolecular binding interactions of vitexin and isovitexin with the interested proteins of tested marker genes. The result of molecular docking to the interested proteins revealed a similar trend with real-time PCR data. In conclusion, EFD potentially enhanced the skin barrier function and hydration of human skin cells.
    Matched MeSH terms: Molecular Structure
  6. Nugroho AE, Komuro T, Kawaguchi T, Shindo Y, Wong CP, Hirasawa Y, et al.
    J Nat Med, 2024 Jan;78(1):68-77.
    PMID: 37690111 DOI: 10.1007/s11418-023-01746-2
    Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a β-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.
    Matched MeSH terms: Molecular Structure
  7. Farabi K, Harneti D, Darwati, Nurlelasari, Mayanti T, Maharani R, et al.
    Nat Prod Res, 2024;38(2):227-235.
    PMID: 35994369 DOI: 10.1080/14786419.2022.2114472
    Three new dammarane-type triterpenoids, namely elliptaglin A-C (1-3) were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume along with three known derivatives, namely (20S)-hydroxydammar-24-en-3-on (4), cabralealactone (5), and E-25-hydroperoxydammar-23-en-20-ol-3-one (6). Subsequently, their chemical structures were determined using HR-ESI-MS, FTIR, 1D and 2D-NMR spectroscopic analysis as well as comparison with previous studies. The cytotoxicity activities of the isolated compounds against MCF-7 breast cancer and B16-F10 melanoma cell lines were then tested using PrestoBlue reagent. The analysis results showed that elliptaglin B (2) had the strongest activity against both cell lines with IC50 values of 60.98 and 51.83 µM, respectively.
    Matched MeSH terms: Molecular Structure
  8. Martula E, Morak-Młodawska B, Jeleń M, Okechukwu PN, Balachandran A, Tehirunavukarasu P, et al.
    Molecules, 2023 Nov 19;28(22).
    PMID: 38005384 DOI: 10.3390/molecules28227662
    Many new isomeric dipyridothiazine dimers have been presented as molecules with anticancer potential. These compounds were obtained in efficient syntheses of 1,6-, 1,8-, 2,7- and 3,6-diazaphenothiazines with selected alkylaromatic linkers. The structures of these compounds has been proven with two-dimensional spectroscopic techniques (COSY, NOESY, HSQC and HMBC) and high-resolution mass spectrometry (HRMS). In silico analyses of probable molecular targets were performed using the Way2Drug server. All new dimers were tested for anticancer activity against breast cancer line MCF7 and colon cancer line SW480. Cytotoxicity was assessed on normal L6 muscle cells. The tested dimers had high anticancer potential expressed as IC50 and the selectivity index SI. The most active derivative, 4c, showed an IC50 activity of less than 1 µM and an SI selectivity index higher than 100. Moreover, the compounds were characterized by low toxicity towards normal cells, simultaneously indicating a high cytostatic potential.
    Matched MeSH terms: Molecular Structure
  9. Ying Y, Tu S, Ni J, Lu X, Hu X, Lei P, et al.
    Fitoterapia, 2023 Oct;170:105662.
    PMID: 37648028 DOI: 10.1016/j.fitote.2023.105662
    Two new terrein derivatives asperterreinones A-B (1-2), one new octahydrocoumarin derivative (±)-asperterreinin A (6), along with seventeen known compounds, were isolated from Aspergillus terreus F6-3, a marine fungus associated with Johnius belengerii. The structures of 1, 2, and 6 were established on the basis of 1D and 2D NMR, mass spectroscopy, comparative electronic circular dichroism (ECD) spectra analysis, density functional theory calculation of 13C NMR, and DP4+ probability analysis. Among all the isolates, eurylene (7), a constituent of the Malaysian medicinal plant Eurycoma longifolia, was obtained from a microbial source for first time. In the in vitro bioassay, 11 and 13 showed potent inhibitory activity against the Escherichia coli β-glucuronidase (EcGUS) with IC50 values of 27.75 ± 0.73 and 17.73 ± 0.81 μM, respectively. It was the first time that questinol (11) and (±)-aspertertone B (13) were reported as potent EcGUS inhibitors.
    Matched MeSH terms: Molecular Structure
  10. Phongphane L, Mohd Radzuan SN, Abu Bakar MH, Che Omar MT, Supratman U, Harneti D, et al.
    Comput Biol Chem, 2023 Oct;106:107938.
    PMID: 37542847 DOI: 10.1016/j.compbiolchem.2023.107938
    In our effort to develop potent anti-hyperglycemic compounds with inhibitory activity against α-amylase and α-glucosidase, a series of novel quinoxaline-isoxazole moieties were synthesized. The novel quinoxaline-isoxazole derivatives were assessed in vitro for their anti-hyperglycemic activities on α-amylase and α-glucosidase inhibitions. The results revealed promising IC50 values compared to acarbose as a positive control for α-amylase and α-glucosidase. Among them, N-Ethyl-7-chloro-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5b showed dual inhibitory with IC50 of 24.0 µM for α-amylase and 41.7 µM for α-glucosidase. In addition, N-Ethyl-7-methoxy-3-((3-(2-chlorophenyl)isoxazol-5-yl)methoxy)quinoxalin-2-amine 5j also had dual bioactivities against α-amylase and α-glucosidase with IC50 of 17.0 and 40.1 µM, respectively. Nevertheless, two more compounds N-Ethyl-7-cyano-3-((3-phenylisoxazol-5-yl)methoxy)quinoxaline-2-amine 5e showed strong mono-inhibition for α-glucosidase with IC50 of 16.6 µM followed by N-Ethyl-7-methoxy-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5 f with IC50 of 18.6 µM. The molecular docking study for α-glucosidase inhibitor provided the binding energy ranging from 8.3 to 9.1 kcal/mol and α-amylase inhibitor showed the binding energy score at 8.4 and 8.5 kcal/mol. The dual inhibitions nature of 5b and 5j were further analyzed and confirmed via molecular dynamics including the stability of the compound, interaction energy, binding free energy, and the interaction residue analysis using the MM-GBSA approach. The results showed that compound 5j was the most potent compound. Lastly, the drug-likeness properties were also evaluated with all synthesized compounds 5a-5j and the results reveal that all potent compounds meet Lipinski's rules of five.
    Matched MeSH terms: Molecular Structure
  11. Abbasi MA, Raza H, Aziz-Ur-Rehman, Siddiqui SZ, Muhammad S, Khan FM, et al.
    Chem Biodivers, 2023 Sep;20(9):e202300257.
    PMID: 37578300 DOI: 10.1002/cbdv.202300257
    In the presented work, a new series of three different 4-((3,5-dichloro-2-[(2/4-halobenzyl)oxy]phenyl)sulfonyl)morpholines was synthesized and the structure of these compounds were corroborated by 1 H-NMR & 13 C-NMR studies. The in vitro results established all the three compounds as potent tyrosinase inhibitors relative to the standard. The Kinetics mechanism plots established that compound 8 inhibited the enzyme non-competitively. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0025 μM. Additionally, computational techniques were used to explore electronic structures of synthesized compounds. Fully optimized geometries were further docked with tyrosinase enzyme for inhibition studies. Reasonably good binding/interaction energies and intermolecular interactions were obtained. Finally, drug likeness was also predicted using the rule of five (RO5) and Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. It is anticipated that current experimental and computational investigations will evoke the scientific interest of the research community for the above-entitled compounds.
    Matched MeSH terms: Molecular Structure
  12. Abd Aziz NA, Awang N, Chan KM, Kamaludin NF, Mohamad Anuar NN
    Molecules, 2023 Aug 03;28(15).
    PMID: 37570810 DOI: 10.3390/molecules28155841
    Organotin (IV) dithiocarbamate has recently received attention as a therapeutic agent among organotin (IV) compounds. The individual properties of the organotin (IV) and dithiocarbamate moieties in the hybrid complex form a synergy of action that stimulates increased biological activity. Organotin (IV) components have been shown to play a crucial role in cytotoxicity. The biological effects of organotin compounds are believed to be influenced by the number of Sn-C bonds and the number and nature of alkyl or aryl substituents within the organotin structure. Ligands target and react with molecules while preventing unwanted changes in the biomolecules. Organotin (IV) dithiocarbamate compounds have also been shown to have a broad range of cellular, biochemical, and molecular effects, with their toxicity largely determined by their structure. Continuing the investigation of the cytotoxicity of organotin (IV) dithiocarbamates, this mini-review delves into the appropriate method for synthesis and discusses the elemental and spectroscopic analyses and potential cytotoxic effects of these compounds from articles published since 2010.
    Matched MeSH terms: Molecular Structure
  13. Al-Khdhairawi AAQ, Loo JSE, Abd Mutalib N, Abd Latip N, Manshoor N, Abu Bakar H, et al.
    Phytochemistry, 2023 Jul;211:113685.
    PMID: 37088350 DOI: 10.1016/j.phytochem.2023.113685
    Four previously undescribed alkaloids, aspergillinine A-D, and four known diterpene pyrones were isolated from the potato dextrose agar (PDA) culture of Aspergillus sp. HAB10R12. The chemical structures of the isolated compounds were elucidated based on a detailed analysis of their NMR and MS data. The absolute configuration of the isolated compounds was determined by Electronic Circular Dichroism analysis coupled with computational methods. Aspergillinine A represents the first example of a diketopiperazine dipeptide containing the unnatural amino acid N-methyl kynurenine. Its absolute configuration revealed that it adopts a rather unusual conformation. Aspergillinine B represents a previously unencountered skeleton containing an isoindolinone ring. Aspergillinine C and D were similar to previously isolated diketopiperazine alkaloids, namely, lumpidin and brevianamide F, respectively. The diterpene pyrones were isolated twice previously, once from a soil-derived Aspergillus species, and once from the liquid culture of Aspergillus sp. HAB10R12. The alkaloids isolated in this study showed no antiproliferative activity when tested against HepG2 and A549 cancer cell lines.
    Matched MeSH terms: Molecular Structure
  14. Purnama, Farabi K, Runadi D, Kuncoro H, Harneti D, Nurlelasari, et al.
    Molecules, 2023 Jun 23;28(13).
    PMID: 37446608 DOI: 10.3390/molecules28134946
    The Aglaia genus, a member of the Meliaceae family, is generally recognized to include a number of secondary metabolite compounds with diverse structures and biological activities, including triterpenoids. Among the members of this genus, Aglaia cucullata has been reported to have unique properties and thrives exclusively in mangrove ecosystems. This plant is also known to contain various metabolites, such as flavaglines, bisamides, and diterpenoids, but there are limited reports on the isolation of triterpenoid compounds from its stem bark. Therefore, this research attempted to isolate and elucidate seven triterpenoids belonging to dammarane-type (1-7) from the stem bark of Aglaia cucullata. The isolated compounds included 20S,24S-epoxy-3α,25-dihydroxy-dammarane (1), dammaradienone (2), 20S-hydroxy-dammar-24-en-3-on (3), eichlerianic acid (4), (20S,24RS)-23,24-epoxy-24-methoxy-25,26,27-tris-nor dammar-3-one (5), 3α-acetyl-cabraleahydroxy lactone (6), and 3α-acetyl-20S,24S-epoxy-3α,25-dihydroxydammarane (7). Employing spectroscopic techniques, the chemical structures of the triterpenoids were identified using FTIR, NMR, and HRESITOF-MS. The cytotoxic activity of compounds 1-7 was tested with the PrestoBlue cell viability reagent against MCF-7 breast cancer, B16-F10 melanoma, and CV-1 normal kidney fibroblast cell lines. The results displayed that compound 5 had the highest level of bioactivity compared to the others. Furthermore, the IC50 values obtained were more than 100 μM, indicating the low potential of natural dammarane-type triterpenoids as anticancer agents. These findings provided opportunities for further studies aiming to increase their cytotoxic activities through semi-synthetic methods.
    Matched MeSH terms: Molecular Structure
  15. Mohamed SM, Abou-Ghadir OMF, El-Mokhtar MA, Aboraia AS, Abdel Aal AM
    J Nat Prod, 2023 May 26;86(5):1150-1158.
    PMID: 37098901 DOI: 10.1021/acs.jnatprod.2c00793
    Cancer is often associated with an aberrant increase in tubulin and microtubule activity required for cell migration, invasion, and metastasis. A new series of fatty acid conjugated chalcones have been designed as tubulin polymerization inhibitors and anticancer candidates. These conjugates were designed to harness the beneficial physicochemical properties, ease of synthesis, and tubulin inhibitory activity of two classes of natural components. New lipidated chalcones were synthesized from 4-aminoacetophenone via N-acylation followed by condensation with different aromatic aldehydes. All new compounds showed strong inhibition of tubulin polymerization and antiproliferative activity against breast and lung cancer cell lines (MCF-7 and A549) at low or sub-micromolar concentrations. A significant apoptotic effect was shown using a flow cytometry assay that corresponded to cytotoxicity against cancer cell lines, as indicated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Decanoic acid conjugates were more potent than longer lipid analogues, with the most active being more potent than the reference tubulin inhibitor, combretastatin-A4 and the anticancer drug, doxorubicin. None of the newly synthesized compounds caused any detectable cytotoxicity against the normal cell line (Wi-38) or hemolysis of red blood cells below 100 μM. It is unlikely that the new conjugates described would affect normal cells or interrupt with cell membranes due to their lipidic nature. A quantitative structure-activity relationship analysis was performed to determine the influence of 315 descriptors of the physicochemical properties of the new conjugates on their tubulin inhibitory activity. The obtained model revealed a strong correlation between the tubulin inhibitory activity of the investigated compounds and their dipole moment and degree of reactivity.
    Matched MeSH terms: Molecular Structure
  16. Tang SY, Tan CH, Sim KS, Yong KT, Lim KH, Low YY, et al.
    Phytochemistry, 2023 Apr;208:113587.
    PMID: 36646163 DOI: 10.1016/j.phytochem.2023.113587
    Eight undescribed iboga alkaloids, polyneurines A-H, were isolated from the bark of Tabernaemontana polyneura. The structures of these alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, TDDFT-ECD method, or X-ray diffraction analysis. Polyneurine A possesses a γ-lactone unit embedded within the iboga skeleton, while polyneurines D and E incorporate a formylmethyl moiety at C-3 of the iboga skeleton. Biosynthetic pathways towards the formation of polyneurines A, C, D, and E were proposed.
    Matched MeSH terms: Molecular Structure
  17. Hipolith MM, Khor BK, Hirasawa Y, Murugaiyah V, Lee CY, Morita H, et al.
    Fitoterapia, 2023 Apr;166:105468.
    PMID: 36931528 DOI: 10.1016/j.fitote.2023.105468
    Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1-9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1-12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 μM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.
    Matched MeSH terms: Molecular Structure
  18. Taha M, Rahim F, Zaman K, Anouar EH, Uddin N, Nawaz F, et al.
    J Biomol Struct Dyn, 2023 Mar;41(5):1649-1664.
    PMID: 34989316 DOI: 10.1080/07391102.2021.2023640
    We have synthesized benzo[d]oxazole derivatives (1-21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step via using various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC50 = 0.016 ± 0.12 and 4.5 ± 0.11 µM) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9 and 18 (IC50 = 0.50 ± 0.01, 0.90 ± 0.05 and 0.3 ± 0.05 µM) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18 and 19 (IC50 = 2.70 ± 0.10, 2.60 ± 0.10, 2.20 ± 0.10, 4.25 ± 0.10, 3.30 ± 0.10, 0.96 ± 0.05 and 3.20 ± 0.10 µM) displayed better inhibitory potential than donepezil. Moreover, derivative 18 is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed via a docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as 1H-NMR, 13C-NMR and HREI-MS, respectively.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Molecular Structure
  19. Taha M, Rahim F, Hayat S, Chigurupati S, Khan KM, Imran S, et al.
    Future Med Chem, 2023 Mar;15(5):405-419.
    PMID: 37013918 DOI: 10.4155/fmc-2022-0306
    Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7 μM and 18.15-71.97 μM, respectively, compared with the reference drug, acarbose (11.98 μM and 12.79 μM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 μM, respectively. The structure-activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1-24) were tested for cytotoxicity against the 3T3 mouse fibroblast cell line and were observed to be nontoxic.
    Matched MeSH terms: Molecular Structure
  20. Raza H, Rehman Sadiq Butt A, Athar Abbasi M, Aziz-Ur-Rehman, Zahra Siddiqui S, Hassan M, et al.
    Chem Biodivers, 2023 Feb;20(2):e202201019.
    PMID: 36597268 DOI: 10.1002/cbdv.202201019
    A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a-h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 μM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis.
    Matched MeSH terms: Molecular Structure
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