Displaying publications 1 - 20 of 73 in total

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  1. Almansour AI, Kumar RS, Beevi F, Shirazi AN, Osman H, Ismail R, et al.
    Molecules, 2014 Jul 10;19(7):10033-55.
    PMID: 25014532 DOI: 10.3390/molecules190710033
    A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 μM) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-α-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  2. Ahmad FB, Ghaffari Moghaddam M, Basri M, Abdul Rahman MB
    Biosci. Biotechnol. Biochem., 2010;74(5):1025-9.
    PMID: 20460723
    An easy and efficient strategy to prepare betulinic acid esters with various anhydrides was used by the enzymatic synthesis method. It involves lipase-catalyzed acylation of betulinic acid with anhydrides as acylating agents in organic solvent. Lipase from Candida antarctica immobilized on an acrylic resin (Novozym 435) was employed as a biocatalyst. Several 3-O-acyl-betulinic acid derivatives were successfully obtained by this procedure. The anticancer activity of betulinic acid and its 3-O-acylated derivatives were then evaluated in vitro against human lung carcinoma (A549) and human ovarian (CAOV3) cancer cell lines. 3-O-glutaryl-betulinic acid, 3-O-acetyl-betulinic acid, and 3-O-succinyl-betulinic acid showed IC(50)<10 microg/ml against A549 cancer cell line tested and showed better cytotoxicity than betulinic acid. In an ovarian cancer cell line, all betulinic acid derivatives prepared showed weaker cytotoxicity than betulinic acid.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  3. Kee CH, Ariffin A, Awang K, Takeya K, Morita H, Hussain SI, et al.
    Org Biomol Chem, 2010 Dec 21;8(24):5646-60.
    PMID: 20941451 DOI: 10.1039/c0ob00296h
    The syntheses of fourteen unusual o-carboxamido stilbenes by the Heck protocol revealed surprising complexity related to intriguing substituent effects with mechanistic implications. The unexpected cytotoxic and chemopreventive properties also seem to be substituent dependent. For example, although stilbene 15d (with a 4-methoxy substituent) showed cytotoxicity on HT29 colon cancer cells with an IC(50) of 4.9 μM, the 3,4-dimethoxy derivative (15c) is inactive. It is interesting to observe that the 3,5-dimethoxy derivative (15e) showed remarkable chemopreventive activity in WRL-68 fetal hepatocytes, surpassing the gold standard, resveratrol. The resveratrol concentration needed to be 5 times higher than that of 15e to produce comparable elevation of NQO1.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  4. Abu N, Akhtar MN, Ho WY, Yeap SK, Alitheen NB
    Molecules, 2013 Aug 27;18(9):10367-77.
    PMID: 23985955 DOI: 10.3390/molecules180910367
    Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  5. Syam S, Abdelwahab SI, Al-Mamary MA, Mohan S
    Molecules, 2012 May 25;17(6):6179-95.
    PMID: 22634834 DOI: 10.3390/molecules17066179
    Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC₅₀ values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  6. Ng CH, Kong KC, Von ST, Balraj P, Jensen P, Thirthagiri E, et al.
    Dalton Trans, 2008 Jan 28.
    PMID: 18185860 DOI: 10.1039/b709269e
    A series of ternary metal(ii) complexes {M(phen)(edda); 1a (Cu), 1b (Co), 1c (Zn), 1d (Ni); H(2)edda = N,N(')-ethylenediaminediacetic acid} of N,N'-ethylene-bridged diglycine and 1,10-phenanthroline were synthesized and characterized by elemental analysis, FTIR, UV-visible spectroscopy and magnetic susceptibility measurement. The interaction of these complexes with DNA was investigated using CD and EPR spectroscopy. MTT assay results of 1a-1c , screened on MCF-7 cancer cell lines, show that synergy between the metal and ligands results in significant enhancement of their antiproliferative properties. Preliminary results from apoptosis and cell cycle analyses with flow cytometry are reported. seems to be able to induce cell cycle arrest at G(0)/G(1). The crystal structure of 1a is also included.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  7. Jada SR, Subur GS, Matthews C, Hamzah AS, Lajis NH, Saad MS, et al.
    Phytochemistry, 2007 Mar;68(6):904-12.
    PMID: 17234223
    The plant Andrographis paniculata found throughout Southeast Asia contains Andrographolide 1, a diterpenoid lactone, which has antitumour activities against in vitro and in vivo breast cancer models. In the present study, we report on the synthesis of andrographolide derivatives, 3,19-isopropylideneandrographolide (2), 14-acetyl-3,19-isopropylideneandrographolide (3) and 14-acetylandrographolide (4), and their in vitro antitumour activities against a 2-cell line panel consisting of MCF-7 (breast cancer cell line) and HCT-116 (colon cancer cell line). Compounds 2 and 4 were also screened at the US National Cancer Institute (NCI) for their activities against a panel of 60 human cancer cell lines derived from nine cancer types. Compound 2 was found to be selective towards leukaemia and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian and renal cancer cells at all the dose-response parameters. Compounds 2 and 4 showed non-specific phase of the cell cycle arrest in MCF-7 cells treated at different intervals with different concentrations. NCI's COMPARE and SOM mechanistic analyses indicated that the anticancer activities of these new class of compounds were not similar to that of standard anticancer agents, suggesting novel mechanism(s) of action.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  8. Hussin Y, Aziz MNM, Che Rahim NF, Yeap SK, Mohamad NE, Masarudin MJ, et al.
    Int J Mol Sci, 2018 Apr 11;19(4).
    PMID: 29641445 DOI: 10.3390/ijms19041151
    Extensive research has been done in the search for innovative treatments against colon adenocarcinomas; however, the incidence rate of patients remains a major cause of cancer-related deaths in Malaysia. Natural bioactive compounds such as curcumin have been substantially studied as an alternative to anticancer drug therapies and have been surmised as a potent agent but, nevertheless, remain deficient due to its poor cellular uptake. Therefore, efforts now have shifted toward mimicking curcumin to synthesize novel compounds sharing similar effects. A synthetic analog, (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-ene-1-one (DK1), was recently synthesized and reported to confer improved bioavailability and selectivity toward human breast cancer cells. This study, therefore, aims to assess the anticancer mechanism of DK1 in relation to the induction of in vitro cell death in selected human colon cancer cell lines. Using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, the cytotoxicity of DK1 towards HT29 and SW620 cell lines were investigated. Acridine orange/propidium iodide (AO/PI) dual-staining assay and flow cytometry analyses (cell cycle analysis, Annexin/V-FITC and JC-1 assays) were incorporated to determine the mode of cell death. To further determine the mechanism of cell death, quantitative real-time polymerase chain reaction (qRT-PCR) and proteome profiling were conducted. Results from this study suggest that DK1 induced changes in cell morphology, leading to a decrease in cell viability and subsequent induction of apoptosis. DK1 treatment inhibited cell viability and proliferation 48 h post treatment with IC50 values of 7.5 ± 1.6 µM for HT29 cells and 14.5 ± 4.3 µM for SW620 cells, causing cell cycle arrest with increased accumulation of cell populations at the sub-G₀/G₁phaseof 74% and 23%, respectively. Flow cytometry analyses showed that DK1 treatment in cancer cells induced apoptosis, as indicated by DNA fragmentation and depolarization of the mitochondrial membrane. qRT-PCR results show significant upregulation in the expression of caspase-9 in both HT29 and SW620 cell lines, further supporting that cell death induction by DK1 is via an intrinsic pathway. These outcomes, therefore, demonstrate DK1 as a potential anticancer agent for colon adenocarcinoma due to its anti-apoptotic attributes.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  9. Li L, Zhang W, Desikan Seshadri VD, Cao G
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):3029-3036.
    PMID: 31328556 DOI: 10.1080/21691401.2019.1642902
    Nowadays, the synthesis and characterization of gold nanoparticles (AuNPs) from plant based extracts and effects of their anticancer have concerned an important interest. Marsdenia tenacissima (MT), a conventional Chinese herbal medicine, has long been used for thousands of years to treat tracheitis, asthma, rheumatism, etc. In this present study, we optimize the reaction of parameters to manage the nanoparticle size, which was categorized by high-resolution transmission electron microscopy (HR-TEM). A different characterization method, for example, UV-visible spectroscopy (UV-vis), fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were performed to consider the synthesized AuNPs getting from the MT leaf extract. The MT-AuNPs were analyzed for their cytotoxicity property against HepG2 cells by MTT analysis. The apoptosis was evaluated by using reactive oxygen species (ROS), migration assay, mitochondrial membrane potential (MMP) and apoptotic protein expression. Interestingly, the findings of our study observed the cytotoxicity effect of synthesized MT-AuNPs at a concentration of 59.62 ± 4.37 μg after 24 hrs treatment. Apoptosis was induced by the MT-AuNPs with enhanced ROS, changed MMP and inhibit the migration assay. Finally, the apoptosis was confirmed by the considerable up-regulation of Bax, caspase-9 and caspase-3, while the anti-apoptotic protein expressions of Bcl-2 and Bcl-XL were down-regulated. Although, in this studies, we evaluated the characterization, synthesis and anticancer action of gold nanoparticles from MT (MT-AuNPS) helpful for liver cancer therapeutics.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  10. Lee KY, Ng YL, Wang WS, Ng PY, Chan CW, Lai JW, et al.
    Dalton Trans, 2019 Apr 09;48(15):4987-4999.
    PMID: 30916098 DOI: 10.1039/c9dt00506d
    Chiral enantiomers [Cu(phen)(l-ser)(H2O)]NO31 and [Cu(phen)(d-ser)(H2O)]NO32 (ser = serinato) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(ii) complexes, viz. l- and d-[Cu(phen)(OCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; OCA = oxazolidine-4-carboxylate; x = 1/2, 0-2) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. The crystal structures of 1 and 3 showed both the cationic complexes to have a square pyramidal geometry. These complexes were about nine fold more potent than cisplatin against metastatic MDA-MB-231 breast cancer cells, inducing apoptotic cell death via ROS generation and a massive drop in mitochondrial membrane potential. The results of monitoring EZH1, EZH2 and H3K27me3 revealed that the mode of action of 1-4 also involved the downregulation of EZH2 and it seemed to be independent of the H3K27me3 status.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  11. Yeo CI, Ooi KK, Akim AM, Ang KP, Fairuz ZA, Halim SN, et al.
    J Inorg Biochem, 2013 Oct;127:24-38.
    PMID: 23850666 DOI: 10.1016/j.jinorgbio.2013.05.011
    The Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), compounds are significantly cytotoxic to the HT-29 cancer cell line with 1 being the most active. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis is demonstrated and both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. Compound 1 activates the p73 gene, whereas each of 2 and 3 activates the p53 gene. An additional apoptotic mechanism is exhibited by 2, that is, via the JNK/MAP pathway.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  12. Agbo EN, Makhafola TJ, Choong YS, Mphahlele MJ, Ramasami P
    Molecules, 2015 Dec 25;21(1):E28.
    PMID: 26712730 DOI: 10.3390/molecules21010028
    Suzuki-Miyaura cross-coupling of 6-bromo-2-styrylquinazolin-4(3H)-ones with arylboronic acids afforded a series of novel 6-aryl-2-styrylquinazolin-4(3H)-ones. These compounds were evaluated for potential anticancer properties against the human renal (TK-10), melanoma (UACC-62) and breast cancer (MCF-7) cell lines. Their antimicrobial properties were also evaluated against six Gram-positive and four Gram-negative bacteria, as well as two strains of fungi. Molecular docking studies (in silico) were conducted on compounds 5a, b, d and 6a, b, d-f to recognize the hypothetical binding motif of the title compounds within the active site of the dihydrofolate reductase and thymidylate synthase enzymes.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  13. Asif M, Iqbal MA, Hussein MA, Oon CE, Haque RA, Khadeer Ahamed MB, et al.
    Eur J Med Chem, 2016 Jan 27;108:177-187.
    PMID: 26649905 DOI: 10.1016/j.ejmech.2015.11.034
    The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  14. Iqbal MA, Haque RA, Ahamed SA, Jafari SF, Khadeer Ahamed MB, Abdul Majid AM
    Med Chem, 2015;11(5):473-81.
    PMID: 25553509
    Azolium (imidazolium and benzimidazolium) salts are known as stable precursors for the synthesis of Metal-N-Heterocyclic Carbene (M-NHC) complexes. Recently, some reports have been compiled indicating that benzimidazolium salts have anticarcinogenic properties. The current research is the further investigation of this phenomenon. Three ortho-xylene linked bis-benzimidazolium salts (1-3) with octyl, nonyl and decyl terminal chain lengths have been synthesized. Each of the compounds was characterized using FT-IR and NMR spectroscopic techniques. The molecular geometries of two of the salts (1-2) have been established using X-ray crystallographic technique. The compounds were tested for their cytotoxic properties against three cancerous cell lines namely, human colon cancer (HCT 116), human colorectal adenocarcinoma (HT- 29) and human breast adenocarcinoma (MCF-7). Mouse embryonic fibroblast (3T3-L1) was used as the model cell line of normal cells. The compounds showed selective anti-proliferative activities against the colorectal carcinoma cells. For HCT 116 and HT-29 cells, the IC50 values ranged 0.9-2.6 µM and 4.0-10.0 µM, respectively. The salts 1 and 3 displayed moderate cytotoxicity against the breast cancer (MCF-7) cells with IC50 58.2 and 13.3 µM, respectively. However, the salt 2 produced strong cytotoxicity against MCF-7 cells with IC50 4.4 µM. Interestingly, the compounds demonstrated poor cytotoxic effects towards the normal cells (3T3-L1) as the IC50 was found to be as high as 48.0 µM. Salts 2 and 3 demonstrated more pronounced anti-proliferative effect than the standard drugs used (5-Flourouracil and Tamoxifen).
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  15. Rohilla P, Deep A, Kamra M, Narasimhan B, Ramasamy K, Mani V, et al.
    Drug Res (Stuttg), 2014 Oct;64(10):505-9.
    PMID: 24992500 DOI: 10.1055/s-0034-1368720
    A series of N'-(substituted benzylidene)-2-(benzo[d]oxazol-3(2H)-yl)acetohydrazide derivatives was synthesized and evaluated for its in vitro antimicrobial and anticancer activities. Antimicrobial activity results revealed that compound 12 was found to be the most potent antimicrobial agent. Results of anticancer study indicated that the synthesized compounds exhibited average anticancer potential. Compound 7 (IC 50 =3.12 µM) and compound 16 (IC 50 =2.88 µM) were found to be most potent against breast cancer (MCF7) cell lines. In conclusion, compound 12 and 16 have the potential to be selected as lead compound for the developing of novel antimicrobial and anticancer agents respectively.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  16. Ali AQ, Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AM
    PMID: 24607427 DOI: 10.1016/j.saa.2014.01.086
    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  17. Namvar F, Rahman HS, Mohamad R, Baharara J, Mahdavi M, Amini E, et al.
    Int J Nanomedicine, 2014;9:2479-88.
    PMID: 24899805 DOI: 10.2147/IJN.S59661
    Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 μg/mL (HepG2), 18.75±2.1 μg/mL (MCF-7), 12.5±1.7 μg/mL (HeLa), and 6.4±2.3 μg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  18. Al-Mudaris ZA, Majid AS, Ji D, Al-Mudarris BA, Chen SH, Liang PH, et al.
    PLoS One, 2013;8(11):e80983.
    PMID: 24260527 DOI: 10.1371/journal.pone.0080983
    Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy)-3-methoxybenzaldehyde) compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl)-2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2XP, and (R) and (S)-1-(2-benzyloxy-3-methoxyphenyl)-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1), the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1) has weak anticancer activity even after it was combined with the benzimidazole (2MP), but after addition of another benzylvanillin structure (2XP), stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS) significantly improved the anticancer activity of Bn1. The present study provides a new insight of benzyl vanillin derivatives as potential anti-leukemic agent.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  19. 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: Antineoplastic Agents/chemical synthesis
  20. Jamaludin NS, Goh ZJ, Cheah YK, Ang KP, Sim JH, Khoo CH, et al.
    Eur J Med Chem, 2013 Sep;67:127-41.
    PMID: 23856069 DOI: 10.1016/j.ejmech.2013.06.038
    The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
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