Displaying publications 21 - 40 of 91 in total

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  1. 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*
  2. Fulltext Characterisation of sol-gel method synthesised MgZnFe2O4 nanoparticles and its cytotoxic effects on breast cancer cell line, MDA MB-231 in vitro
    Nordin N, Kanagesan S, Zamberi NR, Yeap SK, Abu N, Tamilselvan S, et al.
    IET Nanobiotechnol, 2017 Apr;11(3):343-348.
    PMID: 28476993 DOI: 10.1049/iet-nbt.2016.0007
    In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol-gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X-ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17-41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB-231) and (MCF-7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB-231 and MCF-7 after being examined with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB-231 cell line than in MCF-7. Therefore, further cytotoxicity tests were performed on MDA MB-231 cell line.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  3. Fulltext Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy
    Yusoh NA, Ahmad H, Gill MR
    ChemMedChem, 2020 Nov 18;15(22):2121-2135.
    PMID: 32812709 DOI: 10.1002/cmdc.202000391
    Platinum drugs are heavily used first-line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA-binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single-strand break damage for synergistic cancer cell killing. In this review, we summarise early-stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti-cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  4. 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
  5. Crystal Structures and Cytotoxicity of Ortho-Xylene Linked Bis-benzimidazolium Salts
    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
  6. Fulltext Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract
    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
  7. Cytotoxicity, alpha-glucosidase inhibition and molecular docking studies of hydroxamic acid chromium(III) complexes
    Hassan LR, Anouar EH, Bahron H, Abdullah F, Mohd Tajuddin A
    J Biol Inorg Chem, 2020 03;25(2):239-252.
    PMID: 31974764 DOI: 10.1007/s00775-020-01755-6
    Hydroxamic acids [R(CO)N(OH)R'] are flexible compounds for organic and inorganic analyses due to their frailer structures compared to the carboxylic acid. The syntheses and characterization of benzohydroxamic acid (BHA), its CH3-, OCH3-, Cl- para-substituted derivatives and their Cr(III) complexes are reported herein. The metal complexes were synthesized by reacting the hydroxamic acids with chromium(III) chloride hexahydrate in 2:1 molar ratio. The compounds were characterized via melting point, elemental analysis, FTIR, 1H and 13C NMR, TGA, mass spectrometry, molar conductance and UV-Visible. Data analysis suggests that each complex has the Cr(III) center coordinated to the carbonyl and hydroxy oxygen atoms of the hydroxamic acids in bidentate O,O manner and two water molecules to form octahedral geometry. Non-electrolytic behavior of the complexes was shown through their low molar conductivity. Cytotoxicity study against HCT116 and alpha-glucosidase inhibition test revealed that all complexes have higher activity than their parent ligands. Molecular docking study shows that the docking of active complexes is thermodynamically favorable and the inhibition efficiency may depend on the types and the numbers of molecular interactions established in the corresponding stable conformers.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  8. Fulltext DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon Carcinoma Cell Lines In Vitro
    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. 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/chemical synthesis
  10. Design and synthesis of mono and bicyclic tetrapeptides thioester as potent inhibitor of histone deacetylases
    Hoque MA, Islam MS, Islam MN, Kato T, Nishino N, Ito A, et al.
    Amino Acids, 2014 Oct;46(10):2435-44.
    PMID: 25048030 DOI: 10.1007/s00726-014-1800-5
    Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that have an effect on gene regulation. The naturally occurring cyclic depsipeptide FK228 containing disulfide and Largazole possessing thioester functionalities act as pro-drugs and share the same HDAC inhibition mechanism in cell. Inspired from these facts, we have reported bicyclic tetrapeptide disulfide HDAC inhibitors resembling FK228 with potent activity and enhanced selectivity. In the present study, we report the design and synthesis of several mono and bicyclic tetrapeptide thioester HDAC inhibitors that share the inhibition mechanism similar to Largazole. Most of the compounds showed HDAC1 and HDAC4 inhibition and p21 promoting activity in nanomolar ranges. Among these the monocyclic peptides 1, 2 and bicyclic peptide, 4 are notable demanding more advanced research to be promising anticancer drug candidates.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis*
  11. Design and synthesis of newer 1,3,4-oxadiazole and 1,2,4-triazole based Topsentin analogues as anti-proliferative agent targeting tubulin
    Naaz F, Ahmad F, Lone BA, Pokharel YR, Fuloria NK, Fuloria S, et al.
    Bioorg Chem, 2020 01;95:103519.
    PMID: 31884140 DOI: 10.1016/j.bioorg.2019.103519
    A set of two series of 1,3,4-oxadiazole (11a-n) and 1,2,4-Triazole (12a, c, e, g, h, j-n) based topsentin analogues were prepared by replacing imizadole moiety of topsentin through a multistep synthesis starting from indole. All the compounds synthesized were submitted for single dose (10 µM) screening against a NCI panel of 60-human cancer cell lines. Among all cancer cell lines, colon (HCC-2998) and Breast (MCF-7, T-47D) cancer cell lines were found to be more susceptible for this class of compounds. Among the compounds tested, compounds 11a, 11d, 11f, 12e and 12h, were exhibited good anti-proliferative activity against various cancer cell lines. Compounds 11d, 12e and 12h demonstrated better activity with IC50 2.42 µM, 3.06 µM, and 3.30 µM respectively against MCF-7 human cancer cell line than that of the standard drug doxorubicin IC50 6.31 µM. Furthermore, 11d induced cell cycle arrest at G0/G1 phase and also disrupted mitochondrial membrane potential with reducing cell migration potential of MCF-7 cells in dose dependent manner. In vitro microtubule polymerization assays found that compound 11d disrupt tubulin dynamics by inhibiting tubulin polymerization with IC50 3.89 μM compared with standard nocodazole (IC50 2.49 μM). In silico docking studies represented that 11d was binding at colchicine binding site of β-tubulin. Compound 11d emerged as lead molecule from the library of compounds tested and this may serve as a template for further drug discovery.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  12. 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
  13. 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*
  14. Fulltext Dexibuprofen amide derivatives as potential anticancer agents: synthesis, in silico docking, bioevaluation, and molecular dynamic simulation
    Ashraf Z, Mahmood T, Hassan M, Afzal S, Rafique H, Afzal K, et al.
    Drug Des Devel Ther, 2019;13:1643-1657.
    PMID: 31190743 DOI: 10.2147/DDDT.S178595
    BACKGROUND: The amide derivatives of nonsteroidal anti-inflammatory drugs have been reported to possess antitumor activity. The present work describes the synthesis of dexibuprofen amide analogues (4a-j) as potential anticancer agents.

    METHODS: The title amides (4a-j) were obtained by simple nucleophilic substitution reaction of dexibuprofen acid chloride with substituted amines in good yield and chemical structures were confirmed by FTIR, 1H NMR, 13C NMR and mass spectral data.

    RESULTS: The brine shrimp lethality assay results showed that all of the synthesized compounds are non-toxic to shrimp larvae. The inhibitory effects on tumor growth were evaluated and it was observed that N-(2,5-dichlorophenyl)-2-(4-isobutylphenyl) propionamide (4e) and N-(2-chlorophenyl)-2-(4-isobutylphenyl) propionamide (4g) exhibited excellent antitumor activity compared to all other derivatives. The compound 4e bearing 2,5-dichloro substituted phenyl ring and 4g possesses 2-chloro substituted phenyl ring exhibited 100% inhibition of the tumor growth. The anticancer activity was evaluated against breast carcinoma cell line (MCF-7) and it was observed that derivative 4e exhibited excellent growth inhibition of cancer cells with IC50 value of 0.01±0.002 µm, which is better than the standard drugs. The docking studies against breast cancer type 1 susceptibility protein BRCA1 (PDBID 3K0H) exhibited good binding affinities, which are in good agreement with the wet lab results. The compounds 4e and 4g showed the binding energy values of -6.39 and -6.34 Kcal/mol, respectively. The molecular dynamic (MD) simulation was also carried out to evaluate the residual flexibility of the best docking complexes of compounds 4e and 4g. The MD simulation analysis assured that the 4e formed a more stable complex with the target protein than the 4g. The synthesized amide derivatives exhibited were devoid of gastrointestinal side effects and no cytotoxic effects against human normal epithelial breast cell line (MCF-12A) were found.

    CONCLUSION: Based upon our wet lab and dry lab findings we propose that dexibuprofen analogue 4e may serve as a lead structure for the design of more potent anticancer drugs.

    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  15. Double-edged Swords: Diaryl pyrazoline thiazolidinediones synchronously targeting cancer epigenetics and angiogenesis
    Upadhyay N, Tilekar K, Safuan S, Kumar AP, Schweipert M, Meyer-Almes FJ, et al.
    Bioorg Chem, 2021 11;116:105350.
    PMID: 34547645 DOI: 10.1016/j.bioorg.2021.105350
    In the present study, two novel series of compounds incorporating naphthyl and pyridyl linker were synthesized and biological assays revealed 5-((6-(2-(5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethoxy) naphthalene-2-yl)methylene)thiazolidine-2,4-dione (14b) as the most potent dual inhibitors of vascular endothelial growth factors receptor-2 (VEGFR-2) and histone deacetylase 4 (HDAC4). Compounds 13b, 14b, 17f, and 21f were found to stabilize HDAC4; where, pyridyl linker swords were endowed with higher stabilization effects than naphthyl linker. Also, 13b and 14b showed best inhibitory activity on VEGFR-2 as compared to others. Compound 14b was most potent as evident by in-vitro and in-vivo biological assessments. It displayed anti-angiogenic potential by inhibiting endothelial cell proliferation, migration, tube formation and also suppressed new capillary formation in the growing chick chorioallantoic membranes (CAMs). It showed selectivity and potency towards HDAC4 as compared to other HDAC isoforms. Compound 14b (25 mg/kg, i.p.) also indicated exceptional antitumor efficacy on in-vivo animal xenograft model of human colorectal adenocarcinoma (HT-29). The mechanism of action of 14b was also confirmed by western blot.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  16. 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*
  17. Enantiomeric pairs of ternary copper(ii) complexes and their aldol-type condensation products: synthesis, characterization, and anticancer and epigenetic properties
    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
  18. Enhanced photocatalysis and anticancer activity of green hydrothermal synthesized Ag@TiO2 nanoparticles
    Hariharan D, Thangamuniyandi P, Jegatha Christy A, Vasantharaja R, Selvakumar P, Sagadevan S, et al.
    J. Photochem. Photobiol. B, Biol., 2020 Jan;202:111636.
    PMID: 31739259 DOI: 10.1016/j.jphotobiol.2019.111636
    Titanium dioxide (TiO2) nanoparticles (NPs) have been doped with varying amounts (0.005, 0.010 and 0.015 M) of silver nanoparticles (Ag NPs) using hydrothermal method. Further, in this work, a green approach was followed for the formation of Ag@TiO2 NPs using Aloe vera gel as a capping and reducing agent. The structural property confirmed the presence of anatase phase TiO2. Increased peak intensity was observed while increasing the Ag concentration. Further, the morphological and optical properties have been studied, which confirmed the effective photocatalytic behavior of the prepared Ag@TiO2 NPs. The photocatalytic performance of Ag@TiO2 has been considered for the degradation of picric acid in the visible light region. The concentration at 0.010 M of the prepared Ag@TiO2 has achieved higher photocatalytic performance within 50 min, which could be attributed to its morphological behavior. Similarly, anticancer activity against lung cancer cell lines (A549) was also determined. The Ag@TiO2 NPs generated a large quantity of reactive oxygen species (ROS), resulting in complete cancer cell growth suppression after their systemic in vitro administration. Ag@TiO2 NPs was adsorbed visible light that leads to an enhanced anticancer sensitivity by killing and inhibiting cancer cell reproduction through cell viability assay test. It was clear that 0.015 M of Ag@TiO2 NPs were highly effective against human lung cancer cell lines and showed increased production of ROS in cancer cell lines due to the medicinal behavior of the Aloe vera gel.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  19. Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3-Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight
    Safdar MH, Hasan H, Afzal S, Hussain Z
    Mini Rev Med Chem, 2018;18(12):1047-1063.
    PMID: 29173165 DOI: 10.2174/1389557517666171123212039
    The immune system is an intricate and coordinated nexus serving as a natural defense to preclude internal and external pathogenic insults. The deregulation in the natural balance of immunological functions as a consequence of either over expression or under expression of immune cells tends to cause disruption of homeostasis in the body and may lead to development of numerous immune system disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well-documented as ideal lead compounds or precursors to design a wide range of pharmacologically active agents to down-regulate various immune disorders. Owing to their unique structural and molecular framework, these α, β-unsaturated carbonyl-based moieties have also gained remarkable recognition due to their other multifarious pharmacological properties including antifungal, anti-inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer potential. Though a great number of methodologies are currently being employed for their synthesis, this review mainly focuses on the natural and synthetic chalcone derivatives that are exclusively synthesized via Claisen-Schmidt condensation reaction and their immunomodulatory prospects. We have critically reviewed the literature and provided convincing evidence for the promising efficacy of chalcone derivatives to modulate functioning of various innate and adaptive immune players including granulocytes, mast cells, monocytes, macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.
    Matched MeSH terms: Antineoplastic Agents/chemical synthesis
  20. 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
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