Displaying publications 221 - 240 of 269 in total

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  1. Antioxidant, cytotoxic activities, and structure-activity relationship of gallic acid-based indole derivatives
    Khaledi H, Alhadi AA, Yehye WA, Ali HM, Abdulla MA, Hassandarvish P
    Arch Pharm (Weinheim), 2011 Nov;344(11):703-9.
    PMID: 21953995 DOI: 10.1002/ardp.201000223
    A new series of gallic hydrazones containing an indole moiety was synthesized through the reaction of gallic hydrazide and different indole carboxaldehydes. Their antioxidant activities were determined on DPPH radical scavenging and inhibition of lipid peroxidation. The in-vitro cytotoxic activities of the compounds were evaluated against HCT-116 (human colon cancer cell line) and MCF-7 (estrogen-dependent human breast cancer cell line) by the MTT method. An attempt to correlate the biological results with their structural characteristics has been done. A limited positive structure activity relationship was found between cytotoxic and antioxidant activities.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  2. Microarray and quantitative PCR analysis of gene expression profiles in response to treatment with tomato leaf extract in mcf-7 breast cancer cells
    Amid A, Wan Chik WD, Jamal P, Hashim YZ
    Asian Pac J Cancer Prev, 2012;13(12):6319-25.
    PMID: 23464452
    We previously found cytotoxic effects of tomato leaf extract (TLE) on the MCF-7 breast cancer cell line. The aim of this study was to ascertain the molecular mechanisms associated with the usage of TLE as an anticancer agent by microarray analysis using mRNA from MCF-7 breast cancer cells after treatment with TLE for 1 hr and 48 hrs. Approximately 991 genes out of the 30,000 genes in the human genome were significantly (p<0.05) changed after the treatment. Within this gene set, 88 were significantly changed between the TLE treated cells and the untreated MCF-7 cells (control cells) with a cut-off fold change >2.00. In order to focus on genes that were involved in cancer cell growth, only twenty-nine genes were selected, either down-regulated or up-regulated after treatment with TLE. Microarray assay results were confirmed by analyzing 10 of the most up and down regulated genes related to cancer cells progression using real-time PCR. Treatment with TLE induced significant up-regulation in the expression of the CRYAB, PIM1, BTG1, CYR61, HIF1-α and CEBP-β genes after 1 hr and 48 hrs, whereas the TXNIP and THBS1 genes were up-regulated after 1 hr of treatment but down-regulated after 48 hrs. In addition both the HMG1L1 and HIST2H3D genes were down-regulated after 1 hr and 48 hrs of treatment. These results demonstrate the potent activity of TLE as an anticancer agent.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  3. Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein
    Ng WK, Yazan LS, Ismail M
    Toxicol In Vitro, 2011 Oct;25(7):1392-8.
    PMID: 21609759 DOI: 10.1016/j.tiv.2011.04.030
    Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  4. Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid
    Seng HL, Von ST, Tan KW, Maah MJ, Ng SW, Rahman RN, et al.
    Biometals, 2010 Feb;23(1):99-118.
    PMID: 19787298 DOI: 10.1007/s10534-009-9271-y
    Crystal structure analysis of the zinc complex establishes it as a distorted octahedral complex, bis(3-methylpicolinato-kappa(2) N,O)(2)(1,10-phenanthroline-kappa(2) N,N)-zinc(II) pentahydrate, [Zn(3-Me-pic)(2)(phen)]x5H(2)O. The trans-configuration of carbonyl oxygen atoms of the carboxylate moieties and orientation of the two planar picolinate ligands above and before the phen ligand plane seems to confer DNA sequence recognition to the complex. It cannot cleave DNA under hydrolytic condition but can slightly be activated by hydrogen peroxide or sodium ascorbate. Circular Dichroism and Fluorescence spectroscopic analysis of its interaction with various duplex polynucleotides reveals its binding mode as mainly intercalation. It shows distinct DNA sequence binding selectivity and the order of decreasing selectivity is ATAT > AATT > CGCG. Docking studies lead to the same conclusion on this sequence selectivity. It binds strongly with G-quadruplex with human tolemeric sequence 5'-AG(3)(T(2)AG(3))(3)-3', can inhibit topoisomerase I efficiently and is cytotoxic against MCF-7 cell line.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  5. Nutrient composition, antioxidant properties, and anti-proliferative activity of Lignosus rhinocerus Cooke sclerotium
    Yap YH, Tan N, Fung S, Aziz AA, Tan C, Ng S
    J Sci Food Agric, 2013 Sep;93(12):2945-52.
    PMID: 23460242 DOI: 10.1002/jsfa.6121
    Lignosus rhinocerus (tiger milk mushroom) is an important medicinal mushroom used in Southeast Asia and China, and its sclerotium can be developed into functional food/nutraceuticals. The nutrient composition, antioxidant properties, and anti-proliferative activity of wild type and a cultivated strain of L. rhinocerus sclerotia were investigated.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  6. Fulltext Clinacanthus nutans (Burm. f.) Lindau Ethanol Extract Inhibits Hepatoma in Mice through Upregulation of the Immune Response
    Huang D, Guo W, Gao J, Chen J, Olatunji JO
    Molecules, 2015;20(9):17405-28.
    PMID: 26393569 DOI: 10.3390/molecules200917405
    Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ⁺ T cells and decreased the number of IL-4⁺ T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  7. Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks correlate with activity; synthesis of 5F203 hydrogels for local delivery
    Stone EL, Citossi F, Singh R, Kaur B, Gaskell M, Farmer PB, et al.
    Bioorg Med Chem, 2015 Nov 01;23(21):6891-9.
    PMID: 26474663 DOI: 10.1016/j.bmc.2015.09.052
    Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R(2)>0.7). Time-dependent appearance of γ-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  8. Fulltext Novel sesquiterpene lactone analogues as potent anti-breast cancer agents
    Nakagawa-Goto K, Chen JY, Cheng YT, Lee WL, Takeya M, Saito Y, et al.
    Mol Oncol, 2016 06;10(6):921-37.
    PMID: 27055598 DOI: 10.1016/j.molonc.2016.03.002
    Triple-negative breast cancer (TNBC) is associated with high grade, metastatic phenotype, younger patient age, and poor prognosis. The discovery of an effective anti-TNBC agent has been a challenge in oncology. In this study, fifty-eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD-35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA-MB-231, without inhibiting normal mammary cells M10. DETD-35 exhibited a better effect than parental DET on inhibiting migration, invasion, and motility of MDA-MB-231 cells in a concentration-dependent manner. Comparative study of DETD-35, DET and chemotherapeutic drug paclitaxel (PTX) showed that PTX mainly caused a typical time-dependent G2/M cell-cycle arrest, while DETD-35 or DET treatment induced cell apoptosis. In vivo efficacy of DETD-35 was evaluated using a lung metastatic MDA-MB-231 xenograft mouse model. DETD-35 significantly suppressed metastatic pulmonary foci information along with the expression level of VEGF and COX-2 in SCID mice. DETD-35 also showed a synergistic antitumor effect with PTX in vitro and in vivo. This study suggests that the novel compound DETD-35 may have a potential to be further developed into a therapeutic or adjuvant agent for chemotherapy against metastatic TNBC.
    Matched MeSH terms: Antineoplastic Agents/chemistry*
  9. Decreased apoptosis repressor with caspase recruitment domain confers resistance to sunitinib in renal cell carcinoma through alternate angiogenesis pathways
    Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, et al.
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):47-53.
    PMID: 26995091 DOI: 10.1016/j.bbrc.2016.03.048
    Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  10. PNMA2 mediates heterodimeric interactions and antagonizes chemo-sensitizing activities mediated by members of PNMA family
    Lee YH, Pang SW, Tan KO
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):224-229.
    PMID: 27003254 DOI: 10.1016/j.bbrc.2016.03.083
    PNMA2, a member of the Paraneoplastic Ma Family (PNMA), was identified through expression cloning by using anti-sera from patients with paraneoplastic disorder. Tissue expression studies showed that PNMA2 was predominantly expressed in normal human brain; however, the protein was shown to exhibit abnormal expression profile as it was found to be expressed in a number of tumour tissues obtained from paraneopalstic patients. The abnormal expression profile of PNMA2 suggests that it might play an important role in tumorigenesis; however, apart from protein expression and immunological studies, the physiological role of PNMA2 remains unclear. In order to determine potential role of PNMA2 in tumorigenesis, and its functional relationship with PNMA family members, MOAP-1 (PNMA4) and PNMA1, expression constructs encoding the respective proteins were generated for both in vitro and in vivo studies. Our investigations showed that over-expressed MOAP-1 and PNMA1 promoted apoptosis and chemo-sensitization in MCF-7 cells as evidenced by condensed nuclei and Annexin-V positive MCF-7 cells; however, the effects mediated by these proteins were significantly inhibited or abolished when co-expressed with PNMA2 in MCF-7 cells. Furthermore, co-immunoprecipitation study showed that PNMA1 and MOAP-1 failed to associate with each other but readily formed respective heterodimer with PNMA2, suggesting that PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  11. Fulltext In vivo antitumor and antimetastatic effects of flavokawain B in 4T1 breast cancer cell-challenged mice
    Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, et al.
    Drug Des Devel Ther, 2015;9:1401-17.
    PMID: 25834398 DOI: 10.2147/DDDT.S67976
    Flavokawain B (FKB) is a naturally occurring chalcone that can be isolated through the root extracts of the kava-kava plant (Piper methysticum). It can also be synthesized chemically to increase the yield. This compound is a promising candidate as a biological agent, as it is reported to be involved in a wide range of biological activities. Furthermore, FKB was reported to have antitumorigenic effects in several cancer cell lines in vitro. However, the in vivo antitumor effects of FKB have not been reported on yet. Breast cancer is one of the major causes of cancer-related deaths in the world today. Any potential treatment should not only impede the growth of the tumor, but also modulate the immune system efficiently and inhibit the formation of secondary tumors. As presented in our study, FKB induced apoptosis in 4T1 tumors in vivo, as evidenced by the terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining of the tumor. FKB also regulated the immune system by increasing both helper and cytolytic T-cell and natural killer cell populations. In addition, FKB also enhanced the levels of interleukin 2 and interferon gamma but suppressed interleukin 1B. Apart from that, FKB was also found to inhibit metastasis, as evaluated by clonogenic assay, bone marrow smearing assay, real-time polymerase chain reaction, Western blot, and proteome profiler analysis. All in all, FKB may serve as a promising anticancer agent, especially in treating breast cancer.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  12. New pyrimidine-benzoxazole/benzimidazole hybrids: Synthesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition
    Abdelgawad MA, Bakr RB, Ahmad W, Al-Sanea MM, Elshemy HAH
    Bioorg Chem, 2019 11;92:103218.
    PMID: 31536956 DOI: 10.1016/j.bioorg.2019.103218
    To enhance the cytotoxicity of benzimidazole and/or benzoxazole core, the benzimidazole/benzoxazole azo-pyrimidine were synthesized through diazo-coupling of 3-aminophenybenzimidazole (6a) or 3-aminophenylbenzoxazole (6b) with diethyl malonate. The new azo-molanates 6a&b mixed with urea in sodium ethoxide to afford the benzimidazolo/benzoxazolopyrimidine 7a&b. The structure elucidation of new synthesized targets was proved using spectroscopic techniques NMR, IR and elemental analysis. The cytoxicity screening had been carried out against five cancer cell lines: prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), pancreas cancer (PaCa-2) and colon cancer (HT-29). Furthermore, the antioxidant activity, phospholipase A2-V and cyclooxygenases inhibitory activities of the target compounds 7a&b were evaluated and the new compounds showed potent activity (cytotoxicity IC50 range from 4.3 to 9.2 µm, antioxidant activity from 40% to 80%, COXs or LOX inhibitory activity from 1.92 µM to 8.21 µM). The docking of 7a&b was made to confirm the mechanism of action.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  13. Design, Synthesis and Therapeutic Potential of Some 6, 6'-(1,4- phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine)analogues
    Kumar S, Narasimhan B, Lim SM, Ramasamy K, Mani V, Shah SAA
    Mini Rev Med Chem, 2019;19(7):609-621.
    PMID: 30526456 DOI: 10.2174/1389557519666181210162413
    BACKGROUND: A series of 6, 6'-(1,4-phenylene)bis(4-(4-bromophenyl)pyrimidin-2-amine) derivatives has been synthesized by Claisen-Schmidt condensation and its chemical structures was confirmed by FT-IR, 1H/13C-NMR spectral and elemental analyses. The molecular docking study was carried out to find the interaction between active bis-pyrimidine compounds with CDK-8 protein. The in vitro antimicrobial potential of the synthesized compounds was determined against Gram-positive and Gram-negative bacterial species as well fungal species by tube dilution technique. Antimicrobial results indicated that compound 11y was found to be most potent one against E. coli (MICec = 0.67 µmol/mL) and C. albicans (MICca = 0.17 µmol/mL) and its activity was comparable to norfloxacin (MIC = 0.47 µmol/mL) and fluconazole (MIC = 0.50 µmol/mL), respectively.

    CONCLUSION: Anticancer screening of the synthesized compounds using Sulforhodamine B (SRB) assay demonstrated that compounds 2y (IC50 = 0.01 µmol/mL) and 4y (IC50= 0.02 µmol/mL) have high antiproliferative potential against human colorectal carcinoma cancer cell line than the reference drug (5- fluorouracil) and these compounds also showed best dock score with better potency within the ATP binding pocket and may also be used lead for rational drug designing.

    Matched MeSH terms: Antineoplastic Agents/chemistry*
  14. Suppressing growth, migration, and invasion of human hepatocellular carcinoma HepG2 cells by Catharanthus roseus‑silver nanoparticles
    Azhar NA, Ghozali SZ, Abu Bakar SA, Lim V, Ahmad NH
    Toxicol In Vitro, 2020 Sep;67:104910.
    PMID: 32526345 DOI: 10.1016/j.tiv.2020.104910
    Application of silver nanoparticles serves as a new approach in cancer treatment due to its unique features. Biosynthesis of silver nanoparticles using plant is advantageous since they are easily accessible, nontoxic and produce quicker reaction compared to other methods. To evaluate the cytotoxicity, mechanism of cell death and DNA damage of biosynthesized Catharanthus roseus-silver nanoparticles on human liver cancer (HepG2) cells. The antiproliferative activity of Catharanthus roseus‑silver nanoparticles was measured using MTT assay. The cytotoxic effects were further evaluated by measuring nitric oxide and reactive oxygen species (ROS). The mechanism of cell death was determined by annexin-FITC/propidium iodide, mitochondrial membrane potential (MMP) and cell cycle assays. The assessment of DNA damage was evaluated using Comet assay method. The uptake of the nanoparticles were evaluated by Transmission Electron Microscopy (TEM). Catharanthus roseus‑silver nanoparticles has inhibited the proliferation of HepG2 cells in a time-dependent manner with a median IC50 value of 3.871 ± 0.18 μg/mL. The concentration of nitrite and ROS were significantly higher than control. The cell death was due to apoptosis associated with MMP loss, cell cycle arrest, and extensive DNA damage. TEM analysis indicated the presence of free nanoparticles and endosomes containing the nanoparticles. The findings show that Catharanthus roseus‑silver nanoparticles have produced cytotoxic effects on HepG2 cells and thus may have a potential to be used as an anticancer treatment, particularly for hepatocellular carcinoma.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  15. Synthesis, characterization and biological properties of cobalt(II) complexes of 1,10-phenanthroline and maltol
    Chin LF, Kong SM, Seng HL, Khoo KS, Vikneswaran R, Teoh SG, et al.
    J Inorg Biochem, 2011 Mar;105(3):339-47.
    PMID: 21421121 DOI: 10.1016/j.jinorgbio.2010.11.018
    The synthesis and characterization of two cobalt(II) complexes, Co(phen)(ma)Cl 1 and Co(ma)(2)(phen) 2, (phen=1,10-phenanthroline, ma(-)=maltolate or 2-methyl-4-oxo-4H-pyran-3-olate) are reported herein. The complexes have been characterized by FTIR, CHN analysis, fluorescence spectroscopy, UV-visible spectroscopy, conductivity measurement and X-ray crystallography. The number of chelated maltolate ligands seems to influence their DNA recognition, topoisomerase I inhibition and antiproliferative properties.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  16. A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
    Ishak DH, Ooi KK, Ang KP, Akim AM, Cheah YK, Nordin N, et al.
    J Inorg Biochem, 2014 Jan;130:38-51.
    PMID: 24176918 DOI: 10.1016/j.jinorgbio.2013.09.018
    The compound with R=CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R=CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  17. DNA molecular recognition and cellular selectivity of anticancer metal(II) complexes of ethylenediaminediacetate and phenanthroline: multiple targets
    Von ST, Seng HL, Lee HB, Ng SW, Kitamura Y, Chikira M, et al.
    J Biol Inorg Chem, 2012 Jan;17(1):57-69.
    PMID: 21833656 DOI: 10.1007/s00775-011-0829-0
    By inhibiting only two or three of 12 restriction enzymes, the series of [M(phen)(edda)] complexes [M(II) is Cu, Co, Zn; phen is 1,10-phenanthroline; edda is N,N'-ethylenediaminediacetate] exhibit DNA binding specificity. The Cu(II) and Zn(II) complexes could differentiate the palindromic sequences 5'-CATATG-3' and 5'-GTATAC-3', whereas the Co(II) analogue could not. This and other differences in their biological properties may arise from distinct differences in their octahedral structures. The complexes could inhibit topoisomerase I, stabilize or destabilize G-quadruplex, and lower the mitochondrial membrane potential of MCF7 breast cells. The pronounced stabilization of G-quadruplex by the Zn(II) complex may account for the additional ability of only the Zn(II) complex to induce cell cycle arrest in S phase. On the basis of the known action of anticancer compounds against the above-mentioned individual targets, we suggest the mode of action of the present complexes could involve multiple targets. Cytotoxicity studies with MCF10A and cisplatin-resistant MCF7 suggest that these complexes exhibit selectivity towards breast cancer cells over normal ones.
    Matched MeSH terms: Antineoplastic Agents/chemistry*
  18. Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC 6H 4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination
    Ooi KK, Yeo CI, Ang KP, Akim AM, Cheah YK, Halim SN, et al.
    J Biol Inorg Chem, 2015 Jul;20(5):855-73.
    PMID: 26003312 DOI: 10.1007/s00775-015-1271-5
    The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.
    Matched MeSH terms: Antineoplastic Agents/chemistry
  19. Design, Synthesis, SAR Study, Antimicrobial and Anticancer Evaluation of Novel 2-Mercaptobenzimidazole Azomethine Derivatives
    Tahlan S, Narasimhan B, Lim SM, Ramasamy K, Mani V, Shah SAA
    Mini Rev Med Chem, 2020;20(15):1559-1571.
    PMID: 30179132 DOI: 10.2174/1389557518666180903151849
    BACKGROUND: Various analogues of benzimidazole are found to be biologically and therapeutically potent against several ailments. Benzimidazole when attached with heterocyclic rings has shown wide range of potential activities. So, from the above provided facts, we altered benzimidazole derivatives so that more potent antagonists could be developed. In the search for a new category of antimicrobial and anticancer agents, novel azomethine of 2-mercaptobenzimidazole derived from 3-(2- (1H-benzo[d]imidazol-2-ylthio)acetamido)benzohydrazide were synthesized.

    RESULTS AND DISCUSSION: The synthesized analogues were characterized by FT-IR, 1H/13C-NMR and MS studies as well C, H, N analysis. All synthesized compounds were evaluated for in vitro antibacterial activity against Gram-positive (B. subtilis), Gram-negative (E. coli, P. aeruginosa, K. pneumoniae and S. typhi) strains and in vitro antifungal activity against C. albicans and A. niger strains by serial dilution method, the minimum inhibitory concentration (MIC) described in μM/ml. The in vitro anticancer activity of synthesized compounds was determined against human colorectal carcinoma cell line (HCT- 116) using 5-fluorouracil as standard drug.

    CONCLUSION: In general, most of the synthesized derivatives exhibited significant antimicrobial and anticancer activities. Compounds 8, 10, 15, 16, 17, 20 and 22 showed significant antimicrobial activity towards tested bacterial and fungal strains and compound 26 exhibited significant anticancer activity.

    Matched MeSH terms: Antineoplastic Agents/chemistry
  20. In silico studies, synthesis and anticancer activity of novel diphenyl ether-based pyridine derivatives
    Verma R, Bairy I, Tiwari M, Bhat GV, Shenoy GG
    Mol Divers, 2019 Aug;23(3):541-554.
    PMID: 30430400 DOI: 10.1007/s11030-018-9889-1
    A series of novel 2-amino-4-(3-hydroxy-4-phenoxyphenyl)-6-(4-substituted phenyl) nicotinonitriles were synthesized and evaluated against HepG2, A-549 and Vero cell lines. Compounds 3b (IC50 16.74 ± 0.45 µM) and 3p (IC50 10.57 ± 0.54 µM) were found to be the most active compounds against A-549 cell line among the evaluated compounds. Further 3b- and 3p-induced apoptosis was characterized by AO/EB (acridine orange/ethidium bromide) nuclear staining method and also by DNA fragmentation study. A decrease in cell viability and initiation of apoptosis was clearly evident through the morphological changes in the A-549 cells treated with 3b and 3p when stained with this method. Fragmentation of DNA into nucleosomes was observed which further confirmed the cell apoptosis in cells treated with compound 3b. Flow cytometry studies confirmed the cell cycle arrest at G2/M phase in A549 cells treated with compound 3b. Further in silico studies performed supported the in vitro anticancer activity of these compounds as depicted by dock score and binding energy values.
    Matched MeSH terms: Antineoplastic Agents/chemistry
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