Displaying all 14 publications

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  1. Yoon YK, Choon TS
    Arch Pharm (Weinheim), 2016 Jan;349(1):1-8.
    PMID: 26616218 DOI: 10.1002/ardp.201500337
    Benzimidazole derivatives have been shown to possess sirtuin-inhibitory activity. In the continuous search for potent sirtuin inhibitors, systematic changes on the terminal benzene ring were performed on previously identified benzimidazole-based sirtuin inhibitors, to further investigate their structure-activity relationships. It was demonstrated that the sirtuin activities of these novel compounds followed the trend where meta-substituted compounds possessed markedly weaker potency than ortho- and para-substituted compounds, with the exception of halogenated substituents. Molecular docking studies were carried out to rationalize these observations. Apart from this, the methods used to synthesize the interesting compounds are also discussed.
  2. Yoon YK, Oon CE
    Anticancer Agents Med Chem, 2016;16(8):1003-1016.
    PMID: 26961318 DOI: 10.2174/1871520616666160310141622
    The role of sirtuins in age-related diseases is an area of rapidly expanding investigation. Sirtuins are NAD+ -dependent class III histone deacetylases (HDACs) that share extensive homologies with the yeast HDAC Sir2. Class I and class II HDACs inhibitors have been identified as potential anticancer agents and are in clinical studies, but much less is known about class III HDAC inhibitors. However, inhibitors of sirtuins are currently being targeted as potential therapeutic agents for disease such as cancer, neurodegenerative disease and other disorders as sirtuins are discovered to regulate numerous downstream enzymes. Given the link between sirtuins and cancer, understanding the functionality of these enzymes may ultimately have significant impact in cancer prevention or cancer treatment. This review gives an updated overview regarding the regulation of sirtuin enzymes, their implications in cancer, various sirtuin inhibitor scaffolds and their insights in drug design.
  3. Siang LH, Arulsamy A, Yoon YK, Shaikh MF
    Curr Neuropharmacol, 2022;20(10):1925-1940.
    PMID: 34517803 DOI: 10.2174/1570159X19666210913120637
    Epilepsy is a devastating neurological disorder. Current anti-convulsant drugs are only effective in about 70% of patients, while the rest remain drug-resistant. Thus, alternative methods have been explored to control seizures in these drug-resistant patients. One such method may be through the utilization of fruit phytochemicals. These phytochemicals have been reported to have beneficial properties such as anti-convulsant, anti-oxidant, and anti-inflammatory activities. However, some fruits may also elicit harmful effects. This review aims to summarize and elucidate the anti- or pro-convulsant effects of fruits used in relation to seizures in hopes of providing a good therapeutic reference to epileptic patients and their carers. Three databases, SCOPUS, ScienceDirect, and PubMed, were utilized for the literature search. Based on the PRISMA guidelines, a total of 40 articles were selected for critical appraisal in this review. Overall, the extracts and phytochemicals of fruits managed to effectively reduce seizure activities in various preclinical seizure models, acting mainly through the activation of the inhibitory neurotransmission and blocking the excitatory neurotransmission. Only star fruit has been identified as a pro-convulsant fruit due to its caramboxin and oxalate compounds. Future studies should focus more on utilizing these fruits as possible treatment strategies for epilepsy.
  4. Yoon YK, Ali MA, Wei AC, Shirazi AN, Parang K, Choon TS
    Eur J Med Chem, 2014 Aug 18;83:448-54.
    PMID: 24992072 DOI: 10.1016/j.ejmech.2014.06.060
    Two series of novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. Among the newly synthesized compounds, compound 4j displayed the best inhibitory activity for SIRT1 (IC50 = 54.21 μM) as well as for SIRT2 (IC50 = 26.85 μM). Cell proliferation assay showed that compound 4j possessed good antitumor activity against three different types of cancer cells derived from colon (HCT-116), breast (MDA-MB-468) and blood-leukemia (CCRF-CEM) with cell viability of 40.0%, 53.2% and 27.2% respectively at 50 μM. Docking analysis of representative compound 4j into SIRT2 indicated that the interaction with receptor was primarily due to hydrogen bonding and π-π stacking interactions.
  5. Yoon YK, Ali MA, Wei AC, Choon TS, Ismail R
    Eur J Med Chem, 2015 Mar 26;93:614-24.
    PMID: 24996257 DOI: 10.1016/j.ejmech.2013.06.025
    A total of 51 novel benzimidazoles were synthesized by a 4-step reaction starting from basic compound 4-fluoro-3-nitrobenzoic acid under relatively mild reaction conditions. The structure of the novel benzimidazoles was confirmed by mass spectra as well as (1)H NMR spectroscopic data. Out of the 51 novel synthesized compounds, 42 of them were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain using BacTiter-Glo™ Microbial Cell Viability (BTG) method. Results of activity screened using Alamar Blue method was also provided for comparison purposes. Two of the novel benzimidazoles synthesized showed moderately good activity with IC50 of less than 15 μM. Compound 5g, ethyl 2-(4-(trifluoromethyl)phenyl)-1-(2-morpholinoethyl)-1H-benzo[d]imidazole-5-carboxylate, was found to be the most active with IC50 of 11.52 μM.
  6. Yoon YK, Ali MA, Wei AC, Choon TS, Osman H, Parang K, et al.
    Bioorg Med Chem, 2014 Jan 15;22(2):703-10.
    PMID: 24387981 DOI: 10.1016/j.bmc.2013.12.029
    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.
  7. Yoon YK, Ali MA, Choon TS, Arshad S, Razak IA
    Acta Crystallogr Sect E Struct Rep Online, 2012 Oct 1;68(Pt 10):o2967-8.
    PMID: 23125749 DOI: 10.1107/S1600536812039268
    The asymmetric unit of the title compound, C(27)H(32)N(4)O(4)·H(2)O, contains two independent benzimidazole-5-carboxyl-ate mol-ecules and two water mol-ecules. In both main mol-ecules, the pyrrolidine rings are in an envelope conformation with a methyl-ene C atom as the flap. The morpholine rings adopt chair conformations. Both benzimidazole rings are essentially planar, with maximum deviations of 0.008 (1) Å, and form dihedral angles of 37.65 (6) and 45.44 (6)° with the benzene rings. In one mol-ecule, an intra-molecular C-H⋯O hydrogen bond forms an S(7) ring motif. In the crystal, O-H⋯O and O-H⋯N hydrogen bonds connect pairs of main mol-ecules and pairs of water mol-ecules into two independent centrosymmetric four-compoment aggregates. These aggregates are connect by C-H⋯O hydrogen bonds leading to the formation of a three-dimensional network, which is stabilized by C-H⋯π interactions.
  8. Yoon YK, Ali MA, Tan SC, Rosli MM, Razak IA
    PMID: 23424569 DOI: 10.1107/S1600536813001116
    In the title compound, C(24)H(25)N(3)O(5), the eth-oxy group is disordered over two orientations in a 0.853 (14):0.147 (14) ratio. The benzimadazole ring system (r.m.s. deviation = 0.016 Å) makes a dihedral angle of 35.47 (7)° with the attached benzene ring. The pyrrolidine ring adopts an envelope conformation with a methyl-ene C atom as the flap. In the crystal, inversion dimers linked by pairs of O-H⋯N hydrogen bonds generate R(2) (2)(16) loops. C-H⋯O inter-actions link the dimers into a three-dimensional network.
  9. Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS
    Bioorg Med Chem Lett, 2013 Mar 1;23(5):1383-6.
    PMID: 23352268 DOI: 10.1016/j.bmcl.2012.12.069
    A series of fourteen dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions and were screened for their antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv in HTS (High Throughput Screen). Most of the compounds showed moderate to good activity with MIC of less than 20 μM. Compound 4'-(4-bromophenyl)-1'-methyldispiro[acenaphthylene-1,2'-pyrrolidine-3',2″-indane]-2,1″(1H)-dione (4c) was found to be the most active with MIC of 12.50 μM.
  10. Yoon YK, Ali MA, Wei AC, Choon TS, Khaw KY, Murugaiyah V, et al.
    Bioorg Chem, 2013 Aug;49:33-9.
    PMID: 23886696 DOI: 10.1016/j.bioorg.2013.06.008
    Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as (1)H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC50<10 μM. The highest inhibitory activity (IC50=5.12 μM for AChE and IC50=8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure-activity relationship was discussed.
  11. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Acta Pol Pharm, 2011 May-Jun;68(3):343-8.
    PMID: 21648188
    A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.
  12. Suresh Kumar R, Ashraf Ali M, Osman H, Ismail R, Choon TS, Yoon YK, et al.
    Bioorg Med Chem Lett, 2011 Jul 1;21(13):3997-4000.
    PMID: 21621414 DOI: 10.1016/j.bmcl.2011.05.003
    Hexacyclic derivatives share vital pharmacological properties, considered useful in Alzheimer's disease. The aim of this study was synthesis and its evaluation for acetyl cholinesterase inhibitory activity of novel hexacyclic analogues. Compound 4f, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.72 μmol/L.
  13. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Bioorg Med Chem Lett, 2010 Dec 1;20(23):7064-6.
    PMID: 20951037 DOI: 10.1016/j.bmcl.2010.09.108
    Series of pyrolidine analogues were synthesized and examined as acetylcholinesterase (AChE) inhibitors. Among the compounds, compounds 4k and 6k were the most potent inhibitors of the series. Compound 4k, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.10 μmol/L. Pyrolidine analogues might be potential acetyl cholinesterase agents for AD.
  14. Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS, et al.
    Bioorg Med Chem Lett, 2012 Aug 1;22(15):4930-3.
    PMID: 22749825 DOI: 10.1016/j.bmcl.2012.06.047
    A series of twelve dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis strains using agar dilution method, four of them showed good activity with MIC of less than 1 μM. Compound 4'-[5-(4-fluorophenyl)pyridin-3-yl]-1'-methyldispiro[indan-2,2' pyrrolidine-3',2″-indan]-1,3,1″-trione (4b) was found to be the most active with MIC of 0.1215 and 5.121 μM, respectively.
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