In vivo biological evaluation of sodium salt of ethyl (E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-yl)-3-(4-hydroxyphenyl) acrylate as anticancer agent.

Nowadays, quinoline scaffold is among the most vital construction compounds for the development of new drugs. The purpose of this research is to evaluate the anti-cancer activity of sodium salt of ethyl (E)-2-cyano-3-(7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-yl)-3-(4-hydroxyphenyl) acrylate against Ehrlich ascites carcinoma (EAC) cells residing in female mice's peritoneal cavity. The docking study exhibited a favourable interaction between the compound and the receptors 1MOY and 3KJF of osteopontin and caspase 3, respectively. The compound's sodium salt showed potential antioxidant and anti-cancer effects against Ehrlich ascites carcinoma (EAC) cells in vivo. Herein, the results elucidated that treatment with the compound's sodium salt exerted significant chemopreventive and chemotherapeutic effects, which reduced both EAC cell volume and count. Our results revealed that treatment with the sodium salt of the compound demonstrated a remarkable in vivo apoptotic effect through elevation of the expression of caspase 3 and reduction of osteopontin levels. Histopathological examination confirmed that the compound's sodium salt improved liver and kidney tissues without any apparent adverse effects.

New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study.

Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.

In Vitro Anticancer Evaluation of Some Synthesized 2H-Quinolinone and Halogenated 2H-Quinolinone Derivatives as Therapeutic Agents.

BACKGROUND: Searching for new cytotoxic agents with apoptosis induction may represent a viable strategy for cancer treatment to overcome the increased resistance to available anticancer agents. OBJECTIVE: The purpose of the current study was aimed at preparation and anticancer evaluation of two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives against two cancer cell lines. METHODS: Two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives were prepared and screened for their cytotoxicity against breast MCF-7 and liver HepG-2 cancer cell lines as well as normal breast MCF-10a. RESULTS: The tested molecules revealed good cytotoxicity and selectivity toward cancer cell lines relative to normal cells. These compounds were analyzed by DNA flow cytometry on MCF-7 cells. They were found to cause G2/M phase arrest and induced apoptosis at the pre-G1 phase. In addition, increased caspase 3/7 activity and decreased osteopontin expression verified the apoptotic activity. CONCLUSION: The potent compounds discovered in this study can be a hit for the discovery of new cytotoxic agents and are worthy of further investigation.

In Vivo Biological Evaluation of Ethyl 4-(7-hydroxy-4-methyl-2-oxoquinolin-1- ylamino)-coumarin-3-carboxylate as an Antitumor Agent.

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, as well as the viability of tumor cells and life span prolongation. The total anti-oxidant capacity was evaluated in the liver and kidneys. 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 also carried out. RESULTS: EAC-bearing mice injected with the test compound showed a highly significant decrease in tumor cell viability by 100%, compared to the EAC control. Also, it exhibited significant anti-oxidant and apoptotic agents through the results of total anti-oxidant capacity and apoptosis assays. Confirmed by histological examination, the results of the liver and kidney function tests revealed that the test compound had no harmful effect on either of the organs. The docking investigation disclosed an auspicious interaction between the test compound and the receptor (3HB5). To confirm these results, correlations between different parameters were carried out. It was found that there were significant positive and negative correlations between the parameters. CONCLUSION: Hybrid molecules containing coumarin and quinolinone exhibited a potential antitumor effect against EAC cells by the induction of apoptosis and anti-oxidant 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.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties.

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.

A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies.

A new series of diamide functional compounds has been designed, synthesized and confirmed by spectroscopic methods and elemental analyses. All the synthesized compounds were evaluated for their antiproliferative activity on HepG2 cell line. Compounds 3k and 3l were proved to have potent anticancer activity equipotent or more potent than reference compound Combretastatin A-4. The results of DNA flow cytometry analysis demonstrated cell cycle arrest at G2/M phase. The extent of apoptosis induced by 3k and 3l was also determined. Moreover, the compounds produced a significant reduction in cellular microtubules for microtubule loss and potently inhibited the binding of [3H]colchicine to tubulin. Compounds 3k and 3l were proved to upregulate expression of proteins triggering apoptosis, such as p53, Bax, and decreased Bcl-2 overexpression as well as increased the expression of effector caspase- 3/7.

Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line.

Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show a potent inhibitory activity of cell proliferation and cell cycle arrest at G2/M phase. Compounds 4c, 5e and 7c exhibit low to moderate ß-tubulin polymerization inhibition percentage. Meanwhile, compound 6c displayed excellent ß-tubulin percentage of polymerization inhibition equivalent to that exhibited by podo. In addition, compounds 4c, 5e and 7c show strong topoisomerase (topo) II inhibitory activity in nano-molar concentration, compared to known topo inhibitor as etoposide. Finally, apoptotic inducing activity over MCF-7 of compounds 4c, 5e, 6c and 7c is due to up-regulation of p53, increased Bax/Bcl-2 ratio and caspase3/7 levels 2-fold higher than podo.

Inflammatory Biomarkers of Cardiometabolic Risk in Obese Egyptian Type 2 Diabetics.

Inflammatory biomarkers provide a minimally invasive means for early detection and specific treatment of metabolic syndrome and related disorders. The objective of this work was to search for inflammatory biomarkers of cardiometabolic risk in obese type 2 diabetics. The study was performed on 165 persons attending the medical outpatient clinic of Ismailia General Hospital. Their mean age was (50.69 ± 10.15) years. They were divided into three groups. The control group was composed of 55 non-obese, non-diabetic healthy volunteers, 32 males and 23 females. Two study groups were included in this study: group 2 was composed of 55 obese, non-diabetic subjects, 25 males and 30 females matched for age and gender. All patients including the control were subjected to clinical history taking, a clinical examination for the measurement of body mass index (BMI). Investigations were carried out for fasting blood glucose, fasting serum insulin, insulin resistance (IR), the lipid profile, lipoprotein band lipoprotein phospholipase A2, and non-high-density lipoprotein cholesterol (non-HDL-C). Urea, albumin and creatinine analysis and liver function tests were performed, and a complete blood count (CBC) was taken. Hemoglobin A1C (HbA1C), serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested. There were statistically significant differences among the studied groups in terms of total cholesterol, non-HDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), lipoprotein-associated phospholipase A2 and apolipoprotein B. The inflammatory biomarkers hs-CRP, IL-6 and TNF-α were significantly statistically increased in the study groups by (1.62 ± 0.99, 2.32 ± 1.11), (1.73 ± 1.14, 2.53 ± 1.34), and (1.87 ± 1.09, 2.17 ± 0.89) respectively, where p < 0.01. Significant positive correlation was found between Homeostatic Model Assessment (HOMA)-IR, hs-CRP and IL-6. There was a significant positive correlation between non-HDL and hs-CRP, IL-6 and TNF-α and triglycerides and hs-CRP. In conclusion, in this study, CRP, IL-6, and TNF-α were significantly elevated in obese Egyptian type 2 diabetics and were positively correlated with insulin resistance, non-HDL and triglycerides. These inflammatory biomarkers could help in the premature identification of obese type 2 diabetic patients at high cardiometabolic risk. Additionally, these biomarkers are critical for providing prognostics and the validity of future potential anti-inflammatory therapeutic modalities.

Experimental and spectroscopic studies of charge transfer reaction between sulfasalazine antibiotic drug with different types of acceptors.

The charge-transfer (CT) interactions between the electron donor sulfasalazine (SS) and the acceptors 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), p-chloranil (CHL), picric acid (PA) and iodine have been studied spectrophotometrically in CHCl(3) or CH(3) OH solutions. The formed solid CT complexes were also isolated and characterized through infrared, (1) H-NMR, mass spectra as well as elemental and thermal analysis. The CT complexes were discussed in terms of formation constant (K(CT) ), molar extinction coefficient (ε(CT) ), standard free energy (ΔG°), oscillator strength (f), transition dipole moment (µ), resonance energy (R(N) ) and ionization potential (I(D) ). The stoichiometry of these complexes was found to be 1:1 molar ratio and having the formulae [(SS)(DDQ)], [(SS)(CHL)], [(SS)(PA)] and [(SS)(2) I](+) · I(3) (-) , respectively. The charge transfer interaction was successfully applied to the determination of SS drug using mentioned σ and π-acceptors also, the results obtained herein are satisfactory for estimation of SS compound in the pharmaceutical form.

Spectroscopic characterizations and biological studies on newly synthesized Cu(2+) and Zn(2+) complexes of first and second generation dendrimers.

The novel Cu(II) and Zn(II) complexes of first and second generation poly(propylene amine) dendrimers (PPA), comprising 1,8-naphthalimde units on periphery have been synthesized. These new complexes were characterized by elemental analysis, molar conductivity, spectral methods (IR, (1)H NMR and UV-vis spectra) and thermal analysis (TG and DTG) techniques. From elemental analysis as well as thermal studies it has found that the first generation dendrimer behaves as bidentate ligand and forming chelates with 1:2 (ligand:metal) and 1:4 (ligand:metal) stoichiometry for second generation dendrimer. Different kinetic parameters namely activation energy (DeltaE*), enthalpy of activation (DeltaH*), entropy of activation (DeltaS*) and free energy change of activation (DeltaG*) are calculated using Coats-Redfern equation. The antibacterial activity of dendrimers and their complexes was evaluated against some Gram positive and negative bacteria.

Synthesis and spectroscopic studies of some transition metal complexes of a novel Schiff base ligands derived from 5-phenylazo-salicyladehyde and o-amino benzoic acid.

Cu(II), Mn(II), Ni(II), and Zn(II) metal complexes with novel heterocyclic Schiff base derived from 5-phenyl azo-salicyladehyde and o-amino benzoic acid have been synthesized and characterized on the basis of elemental analyses, electronic, IR, and (1)H NMR spectra, and also by aid of scanning electron microscopy (SEM), X-ray powder diffraction, molar ratio measurements, molar conductivity measurements, and thermogravimetric analyses. It has been found that the Schiff base behaves as neutral tridentate (ONO) ligand forming chelates with 1:1 (metal:ligand) stoichiometry.