Cu(TPZ)2 complex as a promising hypoxia selective cytotoxin in prostate cancer.

Background: Hybridization of coumarin moiety with additional antitumor pharmacophores is an auspicious stratagem to afford precious therapeutic interference for the medication of cancer. Objective: The present study aimed to evaluate the antitumor activity of ethyl 4-(7-hydroxy-4-methyl-2-oxoquinolin-1- ylamino)-coumarin-3-carboxylate against Ehrlich ascites carcinoma (EAC) cells in the peritoneal cavity of female mice. Methodology: Molecular docking was used to predict the binding between the test compound and the receptor of breast cancer mutant 3HB5-oxidoreductase.The viability of tumor cells and life span prolongation. Total antioxidant capacity was evaluated in the liver and kidney. Serum alanine transaminase, aspartate transaminase, albumin, total protein, creatinine, and urea were estimated. The concentrations of Bcl-2 and Bax were measured in the liver and kidney tissues. Histopathological examination of the liver and kidney tissues was carried out. Results: EAC-bearing mice injected with the test compound showed a highly significant decrease in tumor cell viability by 100% compared to EAC control. Also, it exhibited significant antioxidant and apoptotic agents through the results of total antioxidant capacity and apoptosis assays. Confirmed by histological examination, the results of the liver and kidney function tests revealed that the test compound has no harmful effect on both two organs. The docking investigation disclosing an auspicious interaction between the test compound and the receptor (3HB5). To confirm our results, correlations between different parameters were carried out. We found that there were significant positive and negative correlations between parameters. Conclusion: Hybrid molecules containing coumarin and quinolinone exhibited potential antitumor effect against EAC cells by induction of apoptosis and antioxidant activities. Results of liver and kidney function tests and the histopathological study revealed that the administration of the test compound nullified most of the pathological alterations induced by EAC cells in mice. Based on these findings, the test compound can be developed as an effective chemotherapeutic agent.

The present study was designed to determine the phytocomponents of the ethanol extract of N. nucifera seed using GC-MS. The phytochemical screening of the ethanolic extract of N. nucifera seed was performed using Perkin-Elmer Gas Chromatography -Mass Spectroscopy. GC-MS chromatogram of the ethanolic extract of N. nucifera seed showed thirty-eight peaks which indicating the presence of thirty-eight phytochemical constituents. The major phytochemical constituents are lupeol (22.95%), octadecatrienoic acid-2-[(trimethylsilyl)oxy]-1-[[(trimethylsilyl)oxy] methyl]ethyl ester (Z,Z,Z) (7.86%), 2,3-dihydroxypropyl--cis-13-docosenoate (5.35%), oleanolic acid(5.19%), tristrimethylsilyl ether derivative of 1,25-dihydroxyvitamin D2 (3.36%) ,trimethylsilyl derivative of 2-monoolein (3.26%), lucenin 2 (3.02%), lupanol (2.95%), tetraneurin-a-diol (2.78%), carotene-1,1',2,2'-tetrahydro-1,1'-dimethoxy (2.32%), 1-oxo-forskolin (1.99%), oleic acid-3-hydroxypropyl ester (1.78%), oleic acid trimethylsilyl ester (1.69%), betulin (1.61%), à-amyrin-trimethylsilyl ether (1.49%), stigmast-5-en-3-ol-(3á,24S)(1.43%), flavone-4'-OH,5-OH,7-di-O-glucoside (1.11%). Among thirty-eight compounds identified, only twelve were reported to have biological activities. Our results indicate that N. nucifera seed contain various bioactive components.

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Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases ( 4–9 ) were employed in the synthesis of selenium nanoparticle forms ( 4NPs–9NPs ). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound 4 showed effective anti-proliferative activity against MCF-7(IC 50 3.14 ± 0.04 µM), HepG-2(IC 50 1.07 ± 0.03 µM), and A549(IC 50 1.53 ± 0.01 µM) cell lines, while its selenium nanoform 4NPs showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, 4NPs outperformed 4 in selectivity against the Vero cell line by 4.5-fold. Furthermore, 4NPs exhibited strong inhibition of CDK1(IC 50 0.47 ± 0.3 µM) and tubulin polymerase(IC 50 0.61 ± 0.04 µM), outperforming 4 and being comparable to roscovitine (IC 50 0.27 ± 0.03 µM) and combretastatin-A4(IC 50 0.25 ± 0.01 µM), respectively. Moreover, both 4 and 4NPs arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that 4 and 4NPs were able to inhibit CDK1 and tubulin polymerase binding sites.

Heterocyclic compounds have a large spectrum of biological activities including antitumor activity. The present study describes the cytotoxic effect of newly synthesized thiazole derivative (TD2) that can prove effective antitumor activity on both in vivo and in vitro studies. Objective: the essential objective of this research is to prove the cytotoxic effect of newly synthesized thiazole derivative (TD2) up on EAC bearing mice and many kinds of human cell lines. Materials and Methods: Antitumor activity of TD2 was examined on EAC in Swiss albino Mice at dose of 2.5 mg/kg. TD2 was injected for 10 following days after transplantation of tumor. After one day of last dose and 18 hours of fasting, 7 Mice were sacrificed and the remaining was kept to evaluate ILS %. Antitumor activity of TD2 was assessed by inspecting tumor volume, tumor weight, viable cell count and nonviable cell count, hematological, biochemical and antioxidant parameters of mice. Results: TD2 demonstrated an inhibitory effect on both cancer cell lines in vitro and Ehrlich ascites cells in vivo.TD2 increased in life span of Ehrlich–bearing mice compared to control. Cell cycle and flow cytometric analysis revealed that TD2 directed Ehrlich cells toward apoptosis by increasing of P53 expression. Conclusion: It was concluded that TD2 have a potent antitumor activity against Ehrlich ascites carcinoma in mice beside a cytotoxic effect on MCF-7, PC3, HepG2 and HCT-116.