RESUMEN

Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh3)3]. The compounds were characterized by FT-IR, UV-Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications.

Asunto(s)

Antineoplásicos , Caenorhabditis elegans , Complejos de Coordinación , Rutenio , Animales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Rutenio/química , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Línea Celular Tumoral , Mutación , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , ADN/química , Células MCF-7

RESUMEN

Palladium metallates containing 4-oxo-4H-chromene-3-carbaldehyde derived ONS donor Schiff bases were synthesized and their efficacy was tested in the direct amination of diosgenin - a phyto steroid. Based on the pharmacological importance of diosgenin, the obtained derivatives were exposed to study their effect on breast cancer cells where they significantly reduced the growth of cancer cells and left non-malignant breast epithelial cells unaffected. Among the derivatives, D3, D4 and D6 showed a better anti-proliferative effect and further analysis revealed that the D3, D4 and D6 derivatives markedly promoted cell cycle arrest and apoptosis by attenuation of the AKT1 signalling pathway.

Asunto(s)

Diosgenina , Neoplasias , Aminación , Apoptosis , Catálisis , Diosgenina/farmacología , Transducción de Señal

RESUMEN

Four binuclear Ni(II) complexes [[Ni2(H-DEAsal-tsc)2(µ-dppm)]·2Cl (1), [Ni2(DEAsal-mtsc)2(µ-dppm)] (2), [Ni2(DEAsal-etsc)2(µ-dppm)] (3) and [Ni2(DEAsal-ptsc)2(µ-dppm)] (4)] were synthesized from the ligands namely 4(N,N)-diethylaminosalicylaldehyde-4(N)-thiosemicarbazone [H2-DEAsal-tsc] H2L1/4(N,N)-diethylaminosalicylaldehyde-4(N)-methyl thiosemicarbazone [H2-DEAsal-mtsc] H2L2/4(N,N)-diethylaminosalicylaldehyde-4(N)-ethyl thiosemicarbazone [H2-DEAsal-etsc] H2L3/4(N,N)diethylaminosalicylaldehyde-4(N)-phenyl thiosemicarbazone [H2-DEAsal-ptsc] H2L4 and 1,1'-bis(diphenylphosphino)methane (dppm) and characterized by a number of spectro analytical techniques. The molecular structure of complexes [Ni2(H-DEAsal-tsc)2(µ-dppm)]·2Cl (1) and [Ni2(DEAsal-ptsc)2(µ-dppm)] (4) have been confirmed by single crystal X-ray diffraction studies. The analysis indicated that in complex 1, the ligand [H2-DEAsal-tsc] coordinated as monobasic tridentate donor through phenolic oxygen, azomethine nitrogen and thione sulfur atoms. However, in complex 4, the ligand [H2-DEAsal-ptsc] behaved as dibasic tridentate donor with thiolate sulfur coordination. Their ability to bind with Calf Thymus Deoxyribonucleic acid (CT-DNA) and Bovine Serum Albumin (BSA) were analysed spectrometrically. Intercalative interaction of the complexes with DNA was confirmed by ethidium bromide (EB) displacement studies and DNA viscosity measurements. The interaction mechanism of the complexes with BSA was found as static. In vitro antiproliferative studies of the ligands and complexes in A549 (human lung carcinoma cancer), MCF-7 (human breast cancer) and HeLa (human cervical cancer) cell lines witnessed significant cytotoxic nature of the complexes with low IC50 values (in µM) than the standard metallo-drug cisplatin. Further, the results of Lactate Dehydrogenase (LDH) and Nitric oxide (NO) release assays supported the effectiveness of the complexes on the above said cancer cells.

Asunto(s)

Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Neoplasias/tratamiento farmacológico , Níquel/química , Bases de Schiff/química , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/química , Cristalografía por Rayos X , Células HeLa , Humanos , Células MCF-7 , Estructura Molecular , Neoplasias/patología , Unión Proteica , Albúmina Sérica Bovina/metabolismo

RESUMEN

Three tetranuclear (1-3) complexes and a mononuclear (4) palladium(ii) complex were synthesized from 3-acetyl-chromen-2-one Schiff base ligands [H2-3MAC-Rtsc] (where R = H [H2-3MAC-tsc]; CH3[H2-3MAC-mtsc]; C2H5[H2-3MAC-etsc] or C6H5[H2-3MAC-ptsc]) and potassium tetrachloropalladate. Their formation was confirmed by spectroscopic techniques and X-ray crystallographic analysis. Their ability to bind with DNA and albumin was analysed by using absorption and emission titrations. The MTT assay was carried out to analyze the anticancer potential of the ligands and synthesized complexes against HepG2 (human liver cancer) and HT-29 (human colon cancer) cells. In addition, the compounds were less toxic when tested against the human normal keratinocyte cells (HaCaT). Ligands and complexes displayed better cytotoxicity with lower IC50 values than the standard drug cisplatin. Further AO-EB and DAPI staining assays were carried out to detect the mode of cell death induced by the complexes i.e. apoptosis or necrosis. The complex 3 showed better cytotoxicity and was further subjected to flow cytometric analysis. The results suggested that the complex 3 induced apoptotic cell death.

Asunto(s)

Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Cromonas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Cromonas/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Células Hep G2 , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Ligandos , Modelos Moleculares , Estructura Molecular , Imagen Óptica , Bases de Schiff/síntesis química , Bases de Schiff/química , Bases de Schiff/farmacología , Relación Estructura-Actividad

RESUMEN

A series of 3-acetyl-8-methoxycoumarin appended thiosemicarbazones (1-4) was prepared from the reaction of 3-acetyl-8-methoxycoumarin with 4(N)-substituted thiosemicarbazides in a view of ascertaining their biological properties with the change of N-terminal substitution in the thiosemicarbazide moiety. Comprehensive characterization was brought about by various spectral and analytical methods. The molecular structures of all the compounds were determined by single crystal X-ray diffraction analysis. Binding studies with Calf thymus DNA (CT-DNA) and proteins such as Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) indicated an intercalative mode of binding with DNA and static quenching mechanism with proteins. The compounds cleaved plasmid DNA (pBR322) and acted well as free radical scavengers. A good spectrum of antimicrobial activity was observed against four bacterial and five fungal pathogens. The compounds exhibited profound antiproliferative activity on MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines. Assay on human normal keratinocyte cell line HaCaT showed that the compounds were non-toxic to normal cells.

Asunto(s)

Antineoplásicos/farmacología , Cumarinas/farmacología , Bases de Schiff/farmacología , Células A549 , Animales , Antiinfecciosos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antioxidantes/farmacología , Bovinos , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Cumarinas/síntesis química , Cumarinas/química , Cristalografía por Rayos X , ADN/metabolismo , Etidio/química , Humanos , Enlace de Hidrógeno , Concentración 50 Inhibidora , Cinética , L-Lactato Deshidrogenasa/metabolismo , Células MCF-7 , Conformación Molecular , Nitritos/metabolismo , Bases de Schiff/síntesis química , Bases de Schiff/química , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Temperatura , Viscosidad

RESUMEN

New Schiff base ligands are prepared by the condensation of 7-hydroxy-3-formylchromone with semicarbazone and phenyl semicarbazone. The complexation of these ligands with Cu(II) ion is proposed in the light of spectral studies (IR, UV-Vis, 1H NMR, 13C NMR, Mass and ESR). In the complexes 1 and 2, the ligands coordinate to the Cu(II) ion in a neutral fashion via ONO donor atoms. The single crystal XRD studies reveal a slightly distorted square-pyramidal geometry for cationic complex (1) and an octahedral geometry for neutral complex (2). Preliminary biological studies such as DNA and Protein binding are carried out by using absorption and emission titration methods. Observation of intercalative mode of binding with Calf Thymus DNA (CT-DNA) is confirmed by means of viscosity measurements. The micro-environmental changes occurring in Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) are monitored via three dimensional (3D) fluorescence studies. The compounds ability in inhibiting microbial growth is tested against different pathogens. MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines are utilized to check the anticancer potential of the synthesized compounds by using MTT, LDH and NO assays. The results show that complexes 1 and 2 exhibited potent cytotoxic activity over standard drug cisplatin.

Asunto(s)

Antiinfecciosos/síntesis química , Cromonas/química , Complejos de Coordinación/química , Cobre/química , Células A549 , Animales , Antiinfecciosos/farmacología , Cationes/química , Bovinos , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/metabolismo , Complejos de Coordinación/toxicidad , ADN/química , ADN/metabolismo , Hongos/efectos de los fármacos , Humanos , Células MCF-7 , Conformación Molecular , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Unión Proteica , Pseudomonas aeruginosa/efectos de los fármacos , Bases de Schiff/química , Semicarbazonas/química , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo

RESUMEN

New cyclometallated ruthenium(ii) complexes of 3-acetyl-7-methoxycoumarin-4N-substituted thiosemicarbazones were synthesized and characterized by analytical and spectral techniques. The crystal structures of the ligands H2L1-3 and complexes (1, 2 and 4) were confirmed by X-ray crystallography. The analysis showed that the ligands have undergone C-H activation at the C(4) carbon of the pyrone ring and acted in a tridentate fashion by binding through C, N and S atoms. CT-DNA and protein (BSA/HSA) binding studies were carried out to analyze their interaction with biomolecules. Good binding affinity with DNA was observed with intercalative binding mode, which was further confirmed by EB displacement and viscosity measurement studies. The quenching mechanism with BSA/HSA was found to be static. Three dimensional (3D) fluorescence measurements were carried out to validate the micro environmental changes in the serum albumins. Their antioxidant propensity and antimicrobial study insisted that the compounds displayed good spectrum of activity. Evaluation of their anticancer potential against MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines revealed that the complexes exhibited better activity than the ligands and cisplatin. Further, the results of LDH and NO release assays supported the cytotoxic nature of the compounds. The non-toxic nature of the compounds was established by testing against the non-cancerous cell line HaCaT (human normal keratinocyte).