Displaying publications 1 - 20 of 86 in total

Abstract:
Sort:
  1. Benzimidazole derivatives as new α-glucosidase inhibitors and in silico studies
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis; Benzimidazoles/chemistry*
  2. Novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone: a new class of β-glucuronidase inhibitors and in silico studies
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis*; Benzimidazoles/chemistry
  3. Benzimidazole derivatives protect against cytokine-induced apoptosis in pancreatic β-Cells
    Zawawi NK, Rajput SA, Taha M, Ahmat N, Ismail NH, Abdullah N, et al.
    Bioorg Med Chem Lett, 2015 Oct 15;25(20):4672-6.
    PMID: 26330080 DOI: 10.1016/j.bmcl.2015.08.022
    Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.
    Matched MeSH terms: Benzimidazoles/chemical synthesis; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry*
  4. Synthesis, molecular docking studies of hybrid benzimidazole as α-glucosidase inhibitor
    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: Benzimidazoles/chemical synthesis; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry*
  5. Synthesis, in vitro urease inhibitory potential and molecular docking study of Benzimidazole analogues
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry
  6. Fulltext Blood-pressure and cholesterol lowering in persons without cardiovascular disease
    Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al.
    N Engl J Med, 2016 May 26;374(21):2032-43.
    PMID: 27039945 DOI: 10.1056/NEJMoa1600177
    BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
    METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
    RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
    CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
    Note: Malaysia is a study site (Author: Yusoff K)
    Matched MeSH terms: Benzimidazoles/administration & dosage*
  7. Structural Modifications of Benzimidazoles via Multi-Step Synthesis and Their Impact on Sirtuin-Inhibitory Activity
    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.
    Matched MeSH terms: Benzimidazoles
  8. Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis*; Benzimidazoles/metabolism; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry
  9. Synthesis and evaluation of antimycobacterial activity of new benzimidazole aminoesters
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis*; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry
  10. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry
  11. Synthesis, characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors
    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.
    Matched MeSH terms: Benzimidazoles/chemical synthesis; Benzimidazoles/pharmacology*; Benzimidazoles/chemistry*
  12. Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles
    Yeong KY, Tan SC, Mai CW, Leong CO, Chung FF, Lee YK, et al.
    Chem Biol Drug Des, 2018 01;91(1):213-219.
    PMID: 28719017 DOI: 10.1111/cbdd.13072
    Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results.
    Matched MeSH terms: Benzimidazoles
  13. A single centre experience of the efficacy and safety of dabigatran etexilate used for stroke prevention in atrial fibrillation
    Yap LB, Rusani BI, Umadevan D, Muhammad Z, Hussin A, Kaur S, et al.
    J Thromb Thrombolysis, 2014 Jul;38(1):39-44.
    PMID: 24197653 DOI: 10.1007/s11239-013-1020-y
    The use of novel anticoagulants such as dabigatran are increasing. Despite increased risks of intracerebral haemorrhage with warfarin among Asians, there is little published data on dabigatran to assess 'real world' efficacy and safety of dabigatran therapy in Asia. This was a retrospective observational study of patients prescribed dabigatran between 2010 and 2013. Data was available for 510 patients: median age 68 years (range 20-91), median CHA2DS2-VASc score was 2 and median HAS-BLED score was 2. The average follow-up duration of 315 days (range: 1-1,096). The overall discontinuation rate was 16% after a median 252 days of treatment with dabigatran. There were 17 (3.3%) patients with minor bleeding, 2 (0.4%) had major bleeding episodes. 20 patients (3.9%) developed dyspepsia which was the most common side effect. The rate of occurrences of adverse effects and bleeding were lower than those seen in the RE-LY trial. None of the patients had an ischaemic stroke, 1 (0.2%) patient had a haemorrhagic stroke. Out of 510 patients, 158 patients (31%) were switched to dabigatran from warfarin. This showed that patients frequently preferred the dabigatran due to convenience when given a choice to switch from warfarin. We report one of the largest registry of Asian patients. Reassuringly, we found that our cohort had a low rate of rate of ischaemic stroke, low rates of side effects and bleeding with the drug.
    Matched MeSH terms: Benzimidazoles/administration & dosage*; Benzimidazoles/adverse effects
  14. Assessment of gastrointestinal nematode infection, anthelmintic usage and husbandry practices on two small-scale goat farms in Malaysia
    Wong F, Sargison N
    Trop Anim Health Prod, 2018 Mar;50(3):581-587.
    PMID: 29143232 DOI: 10.1007/s11250-017-1472-8
    Haemonchosis is a common problem on goat farms in tropical countries such as Malaysia. Prevention of production losses generally depends on the use of anthelmintic drugs, but is threatened by the emergence of anthelmintic resistance. This study investigates anthelmintic efficacy on small-scale Malaysian goat farms and describes putative risk factors. Adult goats had moderate to high pre-treatment faecal trichostrongyle egg counts, despite being housed on slatted floors and fed on cut-and-carry forage, raising questions about the source of nematode infection. Our results show multiple resistance to benzimidazole and macrocyclic lactone anthelmintic drugs and allow us to discuss the genetic origins of resistance with reference to farm husbandry and management. We conclude that improvement in Malaysian goat production efficiency will require the development of sustainable helminth control strategies, underpinned by a better understanding of the origins and population genetics of anthelmintic resistance.
    Matched MeSH terms: Benzimidazoles/therapeutic use
  15. Fulltext Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine
    Wang XY, Lim-Jurado M, Prepageran N, Tantilipikorn P, Wang de Y
    Ther Clin Risk Manag, 2016;12:585-97.
    PMID: 27110120 DOI: 10.2147/TCRM.S105189
    Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients' quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug-drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug's safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria.
    Matched MeSH terms: Benzimidazoles
  16. Fulltext Anti-proliferation effects of benzimidazole analogues on gastric cancer: structure analysis relationship
    Wan Mohd Ikhtiaruddin, Abdah Md Akim, Hasiah Ab Hamid, Norhaizan Mohd Esa, Norizan Ahmat
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):50-50.
    MyJurnal
    Introduction: Benzimidazole analogues are bicyclic compounds that had been synthesized comprising the fusion of benzene and imidazole. It gains interest in research as it poses numerous therapeutic potential such as anti-ulcer, anti-malarial, anti-helminthic, anti-fungal, anti-inflammatory, and anti-cancer. Hence, this work aims to screen novel benzimidazole analogues using MTT assay for potential anti-proliferation activities on gastric cancer, which is the second cause of cancer-related death. Methods: MTT assay was conducted following standard protocol on HGT-1 gastric cancer cells. Cells were seeded and allowed to attach overnight before being introduced with various con-centration of benzimidazole analogues up to 72 hours and the optical density of the MTT was recorded using 560 nm wavelength. Two-Way ANOVA was used to analyse all data, followed by post-hoc Tukey test and the structure analysis relationship was analysed using MTT result. Results: From five analogues, only compound 4 showed an-ti-proliferation activity with IC50 8.212 ± 0.813 μM at 72 hours. Compound 4 had hydroxyl group at ortho- and para- position and remarkably, compound 2 which contained the hydroxyl group at ortho- and meta- position together with compound 5 which contained the combination of meta- and para- induced proliferation on gastric cancer. Conclusion: Different position of hydroxyl group on the benzene ring gives different activities on gastric cancer and from the experiment, only compound 4 had the anti-proliferative activity.
    Matched MeSH terms: Benzimidazoles
  17. Fulltext Relationship between intraocular pressure lowering effect and chemical structure of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives
    Vassiliev P, Iezhitsa I, Agarwal R, Marcus AJ, Spasov A, Zhukovskaya O, et al.
    Data Brief, 2018 Jun;18:340-347.
    PMID: 29896521 DOI: 10.1016/j.dib.2018.02.067
    This article contains data that relate to the study carried out in the work of Marcus et al. (2018) [1]. Data represent an information about pharmacophore analysis of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives and results of construction of the relationship between intraocular pressure (IOP) lowering activity and hypotensive activity of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives using a multilayer perceptron artificial neural network. In particular, they include the ones listed in this article: 1) table of all pharmacophores of imidazo[1,2-a]benzimidazole and pyrimido[1,2-a]benzimidazole derivatives that showed IOP lowering activity; 2) table of all pharmacophores of the compounds that showed absence of IOP lowering activity; 3) table of initial data for artificial neural network analysis of relationship between IOP activity and hypotensive activity of this chemical series; 4) graphical representation of the best neural network model of this dependence; 5) original txt-file of results of pharmacophore analysis; 6) xls-file of initial data for neural network modeling; 7) original stw-file of results of neural network modeling; 8) original xml-file of the best neural network model of dependence between IOP lowering activity and hypotensive activity of these azole derivatives. The data may be useful for researchers interested in designing new drug substances and will contribute to understanding of the mechanisms of IOP lowering activity.
    Matched MeSH terms: Benzimidazoles
  18. Fulltext Synthesis and biological profile of substituted benzimidazoles
    Vashist N, Sambi SS, Narasimhan B, Kumar S, Lim SM, Shah SAA, et al.
    Chem Cent J, 2018 Dec 01;12(1):125.
    PMID: 30506405 DOI: 10.1186/s13065-018-0498-y
    BACKGROUND: A series of benzimidazole derivatives was developed and its chemical scaffolds were authenticated by NMR, IR, elemental analyses and physicochemical properties. The synthesized compounds were screened for their antimicrobial and antiproliferative activities.

    RESULTS AND DISCUSSION: The synthesized benzimidazole compounds were evaluated for their antimicrobial activity using the tube dilution method and were found to exhibit good antimicrobial potential against selected Gram negative and positive bacterial and fungal species. The compounds were also assessed for their anticancer activity exhibited using the SRB assay and were found to elicit antiproliferative activity against MCF7 breast cancer cell line, which was comparable to the standard drug.

    CONCLUSION: Antimicrobial screening results indicated that compounds 1, 2 and 19 to be promising antimicrobial agents against selected microbial species and comparable to standard drugs which included norfloxacin and fluconazole. The anticancer screening results revealed that compounds, 12, 21, 22 and 29 to show the highest activity against MCF7 and their IC50 values were more potent than 5-fluorouracil.

    Matched MeSH terms: Benzimidazoles
  19. Anticancer activities of a benzimidazole compound through sirtuin inhibition in colorectal cancer
    Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

    Matched MeSH terms: Benzimidazoles/pharmacology*; Benzimidazoles/chemistry*
  20. BZD9L1 sirtuin inhibitor: Identification of key molecular targets and their biological functions in HCT 116 colorectal cancer cells
    Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
    Matched MeSH terms: Benzimidazoles/pharmacology*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links