Displaying publications 1 - 20 of 91 in total

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  1. Fulltext Synthesis, characterization, and anticancer activity of new quinazoline derivatives against MCF-7 cells
    Faraj FL, Zahedifard M, Paydar M, Looi CY, Abdul Majid N, Ali HM, et al.
    ScientificWorldJournal, 2014;2014:212096.
    PMID: 25548779 DOI: 10.1155/2014/212096
    Two new synthesized and characterized quinazoline Schiff bases 1 and 2 were investigated for anticancer activity against MCF-7 human breast cancer cell line. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an IC50 value of 6.246×10(-6) mol/L and 5.910×10(-6) mol/L, respectively, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with 1 and 2 subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS formation. We also found activation of caspases-3/7, -8, and -9 in compounds 1 and 2. Moreover, inhibition of NF-κB translocation in MCF-7 cells treated by compound 1 significantly exhibited the association of extrinsic apoptosis pathway. Acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed significant activity towards MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway and are potential candidate for further in vivo and clinical breast cancer studies.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  2. Synthesis of isatin thiosemicarbazones derivatives: in vitro anti-cancer, DNA binding and cleavage activities
    Ali AQ, Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AM
    Spectrochim Acta A Mol Biomol Spectrosc, 2014 May 5;125:440-8.
    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
  3. Fulltext Conjugation of benzylvanillin and benzimidazole structure improves DNA binding with enhanced antileukemic properties
    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
  4. Semisynthesis and in vitro anticancer activities of andrographolide analogues
    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*
  5. Synthesis of new S-substituted derivatives of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide as suitable antibacterial and anticancer agents with moderate cytotoxicity
    Nazir M, Abbasi MA, Aziz-Ur-Rehman -, Siddiqui SZ, Ali Shah SA, Shahid M, et al.
    Pak J Pharm Sci, 2019 Nov;32(6):2585-2597.
    PMID: 31969290
    In the study presented here, the nucleophilic substitution reaction of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide was carried out with different alkyl/aralkyl halides (5a-r) to form its different S-substituted derivatives (6a-r), as depicted in scheme 1. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR and CHN analysis data. Bacterial biofilm inhibitory activity of all the synthesized compounds was carried out against Bacillus subtilis and Escherichia coli. The anticancer activity of these molecules was ascertained using anti-proliferation (SRB) assay on HCT 116 Colon Cancer Cell lines while the cytotoxicity of these molecules was profiled for their haemolytic potential. From this investigation it was rational that most of the compounds exhibited suitable antibacterial and anticancer potential along with a temperate cytotoxicity.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  6. Challenges associated with the synthesis of unusual o-carboxamido stilbenes by the Heck protocol: Intriguing substituent effects, their toxicological and chemopreventive implications
    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*
  7. Fulltext Synthesis, Biological Evaluation and Molecular Docking Studies of 6-Aryl-2-Styrylquinazolin-4(3H)-Ones
    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*
  8. Fulltext Facile, regio- and diastereoselective synthesis of spiro-pyrrolidine and pyrrolizine derivatives and evaluation of their antiproliferative activities
    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
  9. Fulltext Synthesis of chalcones with anticancer activities
    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*
  10. Fulltext Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives
    El-Faham A, Farooq M, Khattab SN, Abutaha N, Wadaan MA, Ghabbour HA, et al.
    Molecules, 2015;20(8):14638-55.
    PMID: 26287132 DOI: 10.3390/molecules200814638
    Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  11. Fulltext A Bottom-Up Synthesis Approach to Silver Nanoparticles Induces Anti-Proliferative and Apoptotic Activities Against MCF-7, MCF-7/TAMR-1 and MCF-10A Human Breast Cell Lines
    Zulkifli NI, Muhamad M, Mohamad Zain NN, Tan WN, Yahaya N, Bustami Y, et al.
    Molecules, 2020 Sep 22;25(18).
    PMID: 32971740 DOI: 10.3390/molecules25184332
    A bottom-up approach for synthesizing silver nanoparticles (AgNPs-GA) phytomediated by Garcinia atroviridis leaf extract is described. Under optimized conditions, the AgNPs-GA were synthesized at a concentration of 0.1 M silver salt and 10% (w/v) leaf extract, 1:4 mixing ratio of reactants, pH 3, temperature 32 °C and 72 h reaction time. The AgNPs-GA were characterized by various analytical techniques and their size was determined to be 5-30 nm. FTIR spectroscopy indicates the role of phenolic functional groups in the reduction of silver ions into AgNPs-GA and in supporting their subsequent stability. The UV-Visible spectrum showed an absorption peak at 450 nm which reflects the surface plasmon resonance (SPR) of AgNPs-GA and further supports the stability of these biosynthesized nanoparticles. SEM, TEM and XRD diffractogram analyses indicate that AgNPs-GA were spherical and face-centered-cubic in shape. This study also describes the efficacy of biosynthesized AgNPs-GA as anti-proliferative agent against human breast cancer cell lines, MCF-7 and MCF-7/TAMR-1. Our findings indicate that AgNPs-GA possess significant anti-proliferative effects against both the MCF-7 and MCF-7/TAMR-1 cell lines, with inhibitory concentration at 50% (IC50 values) of 2.0 and 34.0 µg/mL, respectively, after 72 h of treatment. An induction of apoptosis was evidenced by flow cytometry using Annexin V-FITC and propidium iodide staining. Therefore, AgNPs-GA exhibited its anti-proliferative activity via apoptosis on MCF-7 and MCF-7/TAMR-1 breast cancer cells in vitro. Taken together, the leaf extract from Garcinia atroviridis was found to be highly capable of producing AgNPs-GA with favourable physicochemical and biological properties.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  12. Fulltext Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116
    Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS
    Molecules, 2021 Jan 13;26(2).
    PMID: 33450878 DOI: 10.3390/molecules26020376
    Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated. Screening on HCT 116 at 48 h showed that berberine (10.30 ± 0.89 µg/mL) is the most effective (lowest IC50 value) telomerase inhibitor compared to boldine (37.87 ± 3.12 µg/mL) and silymarin (>200 µg/mL). Further analyses exhibited that berberine treatment caused G0/G1 phase arrest at 48 h due to high cyclin D1 (CCND1) and low cyclin-dependent kinase 4 (CDK4) protein and mRNA levels, simultaneous downregulation of human telomerase reverse transcriptase (TERT) mRNA and human telomerase RNA component (TERC) levels, as well as a decrease in the TERT protein level and telomerase activity. The effect of berberine treatment on the cell cycle was time dependent as it resulted in a delayed cell cycle and doubling time by 2.18-fold. Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  13. Fulltext Efficient Double Suzuki Cross-Coupling Reactions of 2,5-Dibromo-3-hexylthiophene: Anti-Tumor, Haemolytic, Anti-Thrombolytic and Biofilm Inhibition Studies
    Ikram HM, Rasool N, Zubair M, Khan KM, Abbas Chotana G, Akhtar MN, et al.
    Molecules, 2016 Jul 27;21(8).
    PMID: 27472312 DOI: 10.3390/molecules21080977
    The present study describes several novel 2,5-biaryl-3-hexylthiophene derivatives (3a-i) synthesized via a Pd(0)-catalyzed Suzuki cross-coupling reaction in moderate to good yields. The novel compounds were also analyzed for their anti-thrombolytic, haemolytic, and biofilm inhibition activities. In addition, the anti-tumor activity was also evaluated in vitro for newly-synthesized compounds, where 3-hexyl-2,5-bis(4-(methylthio)phenyl)thiophene exhibited the best anti-tumor activity against 4T1 cells with IC50 value of 16 μM. Moreover, 2,5-bis(4-methylphenyl)-3-hexylthiophene showed the highest activity against MCF-7 cells with an IC50 value of 26.2 μM. On the other hand, the compound 2,5-bis(4-chloropheny)-3-hexylthiophene exhibited excellent biofilm inhibition activity. Furthermore, the compound 2,5-bis(3-chloro-4-fluorophenyl)-3-hexylthiophene also exhibited better anti-thrombolytic and hemolytic activity results as compared to the other newly-synthesized compounds.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  14. Fulltext Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas
    Chelliah SS, Paul EAL, Kamarudin MNA, Parhar I
    Molecules, 2021 Feb 22;26(4).
    PMID: 33671796 DOI: 10.3390/molecules26041169
    Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient's response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  15. Fulltext Novel Gold Nanoparticles Reduced by Sargassum glaucescens: Preparation, Characterization and Anticancer Activity
    Ajdari Z, Rahman H, Shameli K, Abdullah R, Abd Ghani M, Yeap S, et al.
    Molecules, 2016 Mar 01;21(3):123.
    PMID: 26938520 DOI: 10.3390/molecules21030123
    The current study investigated the anticancer properties of gold nanoparticles (SG-stabilized AuNPs) synthesized using water extracts of the brown seaweed Sargassum glaucescens (SG). SG-stabilized AuNPs were characterized by ultraviolet-visible spectroscopy, transmission and scanning electron microscopy, and energy dispersive X-ray fluorescence spectrometry. The SG-stabilized AuNPs were stable and small at 3.65 ± 1.69 nm in size. The in vitro anticancer effect of SG-stabilized AuNPs was determined on cervical (HeLa), liver (HepG2), breast (MDA-MB-231) and leukemia (CEM-ss) cell lines using fluorescence microscopy, flow cytometry, caspase activity determination, and MTT assays. After 72 h treatment, SG-stabilized AuNPs was shown to be significant (p < 0.05) cytotoxic to the cancer cells in a dose- and time-dependent manner. The IC50 values of SG-stabilized AuNPs on the HeLa, HepG2, CEM-ss, MDA-MB-231 cell lines were 4.75 ± 1.23, 7.14 ± 1.45, 10.32 ± 1.5, and 11.82 ± 0.9 μg/mL, respectively. On the other hand, SG-stabilized AuNPs showed no cytotoxic effect towards the normal human mammary epithelial cells (MCF-10A). SG-stabilized AuNPs significantly (p < 0.05) arrest HeLa cell cycle at G2/M phase and significantly (p < 0.05) activated caspases-3 and -9 activities. The anticancer effect of SG-stabilized AuNPs is via the intrinsic apoptotic pathway. The study showed that SG-stabilized AuNPs is a good candidate to be developed into a chemotherapeutic compound for the treatment of cancers especially cervical cancer.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  16. Fulltext 3-Bromo-1-hydroxy-9,10-anthraquinone (BHAQ) inhibits growth and migration of the human breast cancer cell lines MCF-7 and MDA-MB231
    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
  17. 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/chemical synthesis
  18. 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/chemical synthesis*
  19. 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/chemical synthesis
  20. 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/chemical synthesis*
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