Synthesis of Sorafenib-Ruthenium Complexes, Investigation of Biological Activities and Applications in Drug Delivery Systems as an Anticancer Agent.

Sorafenib, a multiple kinase inhibitor, is widely used as a first-line treatment for hepatocellular carcinoma. However, there is a need for more effective alternatives when sorafenib proves insufficient. In this study, we aimed to design a structure that surpasses sorafenib's efficacy, leading us to synthesize sorafenib-ruthenium complexes for the first time and investigate their properties.

Design, synthesis, in vitro, and in silico studies of 1,2,4-triazole-piperazine hybrid derivatives as potential MAO inhibitors.

Monoamine oxidases (MAOs) have become promising drug targets for the development of central nervous system agents. In recent research, it was shown that numerous piperazine derivatives exhibit hMAO inhibitory activity. Therefore, in this study, a novel series of 1,2,4-triazole-piperazine derivatives (5a-j) were designed, synthesized, characterized, and screened for their hMAO-A and hMAO-B inhibitory activities.

Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents.

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4'-dimethyl-2,2'-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates.

Anti-lung Cancer and Anti-angiogenic Activities of New Designed Boronated Phenylalanine Metal Complexes.

Background: Drug design and discovery studies still remain of great importance in the search for more convenient chemotherapeutic to avoid the drug resistance, systemic toxicity or the longterm side effects.

Objective: A series of mononuclear gold (III) and platinum (II) complexes based on 4-dihydroxyboryl- DL-phenylalanine (BPA) was designed and synthesized, for the first time, by using 2, 2'-dipyridyl (L1) and 4, 4'-diaminobibenzyl (L2) ligands. Characterization of the synthesized complexes was achieved by using 1H-NMR, IR, MS and elemental analyses.

Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates.

Trimethoprim, a commonly used antibacterial agent, is widely applied in the treatment of variety of infections in human. A few studies have demonstrated an extensive exposure of man to antibiotics, but there is still a lack of data for cytotoxic effects including nephrotoxicity, gastrointestinal toxicity, hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study was to determine cytotoxic and genotoxic activities of trimethoprim (1), trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic acid dihydrate (3).

The in vitro assessment of dipyridophenazine complexes in H-ras oncogene transformed rat embryo fibroblast 5RP7 cell line.

Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazine ligand, dipyrido[3,2-a:2',3'c] phenazine-platinum(II) complex ([Pt(dppz)Cl]) and dipyrido[3,2-a:2',3'c] phenazine-gold(III) complex ([Au(dppz)Cl]Cl) were determined with MTT (3[4,5-dimetiltiyazol2-yl]-2,5-difeniltetrazolyum bromid) assay on 5RP7 cells.

PO-35 - Designing of the new antithrombotic and also anticancer gold complexes.

Introduction: Drugs which are effective on P2Y12 receptor downregulation may be significantly profitable in more than one way. Firstly, P2Y12 inhibition down regulates HIF1a activity which is important in both angiogenesis and metastasis processes. HIF1a also increases tumour cells' resistance to cytotoxic therapy by increasing their ability to recover from DNA damage; so inhibiting HIF1a activity via P2Y12 pathway both increases cytotoxic activity of chemotherapy and helps in the prevention of tumour spread.

Gold(III) compounds-mediated inhibition of lung cancer cell proliferation.

Research on chemotherapeutics for lung cancer is crucial for designing a new therapeutic strategy against malignant lung tumors. Although radiotherapy and chemotherapy, which are not selective for cancer cells and exert toxic effects on healthy cells, have a limited advantage, they are the primary treatment modalities for non-small lung cancer. In addition to cytotoxicity, resistance of chemotherapeutics results in failure of treatment.

Apoptotic effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats.

We evaluated the effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex ([Au(dppz)Cl2]Cl) on apoptosis during chemically induced hepatocellular carcinoma. 48 male Spraque-Dawley rats were divided into six groups; group I (control), group II [Dimethyl sulfoxide (DMSO)], group III ([Au(dppz)Cl2]Cl), group IV [diethylnitrosamine + Phenobabital (DEN + PB)], group V (DEN + PB + [Au(dppz)Cl2]Cl (2nd week)), and group VI (DEN + PB + [Au(dppz)Cl2]Cl (7th week). The rats in groups IV through VI were administrated with DEN in a single dose of intraperitoneal 175 mg/kg.

Investigation of the pharmacological profiles of dinuclear metal complexes as novel, potent and selective cytotoxic agents against ras-transformed cells.

Around the world scientists try to design successful cures against still incurable diseases, especially cancers. New targets for prevention and new agents for therapy need to be identified. We synthesized novel metal complexes [Au(L1)(L2)Pt]Cl2 and [Ru(L1)2(L2)Pt]Cl2 for determining their cytotoxic and apoptotic effects.

Studies on the cytotoxic, apoptotic and antitumoral effects of Au(III) and Pt(II) complexes of 1, 10-phenanthroline on V79 379A and A549 cell lines.

In the present study, Au(III) and Pt(II) complexes of 1, 10-phenanthroline (phen) were synthesized and used as the test compounds. The structure elucidation of the synthesized compounds was performed by IR, (1)H-NMR and MASS spectroscopic data and the results of elemental analyses. The cytotoxic and apoptotic effects of test compounds were elucidated on V79 379A (Chinese hamster lung fibroblast like) and A549 (human lung carcinoma epithelial like) cell lines.

Cytotoxic and genotoxic effects of [Ru(phi)3]2+ evaluated by Ames/Salmonella and MTT methods.

In this work, we synthesized and evaluated the cytotoxic effect of [Ru(phi)(3)](2+), on rat C6 glioma cell line. Cell viability was determined by assay with 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The mutagenicity of [Ru(phi)(3)](2+) was studied in vitro by using two strains of Salmonella typhimurium with frameshift mutation (TA98) and base-pair substitution mutation (TA100) were used in plate incorporation assay in the absence of metabolic activation.

Synthesis and characterization of a new macrocyclic ligand and its copper (II), cadmium (II), and lead (II) complexes: genotoxic activity of these complexes in cultured human lymphocytes.

A new macrocyclic ligand 1,1'-bis(bis-(6,6'-oxymethylenyl-2,2'-bipyridine) binaphthyl, (L), and its complexes CuL(ClO4)2, CuL(NO3)(2).3H2O, CdL(ClO4)2, and PbL(ClO4)2 have been synthesized and characterized on the basis of IR, 1H NMR, 13C NMR, FAB mass, and elemental analyses. Genotoxicity of these metal complexes has also been investigated by cytokinesis-blocked micronucleus assay in cultured human lymphocytes.

Synthesis and antituberculosis activity of new thiazolylhydrazone derivatives.

The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new thiazolylhydrazone derivatives were synthesized and evaluated for antituberculosis activity. The reaction of thiosemicarbazide with acetophenone derivatives gave 1-(1-arylethylidene)thiosemicarbazide (1).

Synthesis and antifungal activities of some aryl [3-(imidazol-1-yl/triazol-1-ylmethyl) benzofuran-2-yl] ketoximes.

In this study, some aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketones, aryl (3-methyl-benzofuran-2-yl) ketoximes and aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketoximes were synthesised starting from 2-aryloyl-3-methyl-benzofuranes. The structure elucidation of the compounds was performed by IR, 1H-NMR, MASS spectroscopy and elemental analyses. Antifungal activities of the compounds were examined and moderate activity was obtained.

Modification of intracellular free calcium in cultured F2408 embryo fibroblasts by 3-substituted-2-thiohydantoin derivatives.

3-substituted-2-thiohydantoin derivatives were synthesized and their structures elucidated by IR, 1H-NMR spectroscopy and elemental analysis. The cytotoxicity of the 2-thiohydantoin derivatives to rat embryo fibroblasts (F2408) in vitro was determined, and the effects of these compounds on intracellular free Ca2+, [Ca2+]i, were measured by spectrofluorophotometry. Cytotoxicity was determined by metabolic reduction of a tetrazolium salt to a formazan dye (MTT assay).

Synthesis and antimicrobial activities of some new nitroimidazole derivatives.

In this study, some new nitroimidazole derivatives were obtained from 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylamine dihydrochloride (4) and 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (5), which were prepared using metronidazole. Compound 4 was reacted with arylisothiocyanates (6) to obtain 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-arylthioureas (7) and the latter with alpha-bromoacetophenones (8) to give 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-arylimino-4-aryl-4-thiazolines (9). Also 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-phenyl-4-arylideneimidazolin-5-ones (11) were prepared by reaction of 4 with 2-phenyl-4-arylidene-5-oxazolones (10).

Synthesis and antifungal activities of some aryl (3-methyl-benzofuran-2-yl) ketoximes.

In this study, some aryl (3-methyl-benzofuran-2-yl) ketoximes and their ethers and esters were synthesised. The structure elucidation of the compounds was performed by IR, 1H-NMR, MASS spectroscopy and elemental analyses. Antifungal activities of the compounds were examined and moderate activity was obtained.

Synthesis and antifungal activities of some aryl(benzofuran-2-yl)ketoximes.

In this study, some aryl(benzofuran-2-yl)ketoximes and their ethers and esters were synthesised. The structure elucidation of the compounds was performed by IR, 1H NMR and mass spectroscopic data and elemental analyses results. Antifungal activities of the compounds were examined and notable activity was obtained.

Synthesis and antimicrobial activities of some 3-arylamino-5-[2-(substituted 1-imidazolyl)ethyl]-1,2,4-triazole derivatives.

In this study, some 3-arylamino-5-[2-(substituted imidazol-1-yl or benzimidazol-1-yl)ethyl]-1,2,4-triazole derivatives were synthesised by reacting 3-(substituted imidazol-1-yl)propionyl hydrazides, with S-methyl-N'-arylisothiouronium iodide salts. Their structures were elucidated by IR, 1H-NMR and mass spectroscopic data and elemental analyses results. Antimicrobial activities of the compounds were observed against Staphylococcus aureus NRRL B-767, Micrococcus luteus NRRL B-4375, Escherichia coli B, Pseudomonas aeroginosa NRRL B-23 and the fungi Candida albicans and Candida glabrata by using the tube dilution technique.

Some 1-substituted 3-aryl-1,4-dihydro-1,2,4-triazino[4,3-a]-benzimidazoles and their vasodilatory activities.

In this study, some 1-substituted 3-aryl-1,4-dihydro-1,2,4-triazino[4,3-a]benzimidazole derivatives were synthesized, their structures were elucidated, and their vasodilatory activities were examined. It was found that the compounds under investigation showed appreciable vasodilatory activity.

Synthesis of some 3-arylamino-5-aryloxymethyl[1,2,4]triazole derivatives and their antimicrobial activity.

In this study, some 3-arylamino-5-aryloxymethyl[1,2,4]triazole derivatives were synthesized by reacting S-methyl-N'-arylisothiouronium iodide and 2-(aryloxy)alkanoic acid hydrazide. The structural elucidation of the compounds was performed by IR, 1H-NMR and MS spectroscopic data and elemental analyses results. Antibacterial and antifungal activities of the compounds were examined.

Syntheses of some 2,3, 6-trisubstituted quinoxaline derivatives and investigation of their antispasmodic activities.

Some 2, 3, 6-trisubstituted quinoxaline derivatives were synthesized and their antispasmodic activities were determined on the isolated rat ileum. In the synthesis, some dicarbonyl compounds were reacted with substituted or non-substituted o-phenylenediamines in the presence of acetic acid and gained eighteen compounds. All spectral and elemental analyses of the compounds complete and their structures were elucidated.