RESUMEN
As a contribution to the development of novel coumarin-oxime ether conjugates with therapeutically interesting properties, a series of coumarin-oxime ether (1a-1j) was synthesised using SN2 reaction of bromomethyl coumarins with butane-2,3-dione monoxime. Invitro anti-tuberculosis activityagainstMTBH37Rv strain was established for the coumarin-oxime ether (1a-1j). Most of the compounds exhibited significant activity with minimum inhibitory concentration (MIC)in the range of 0.04-3.12⯵gâ¯mL-1. Compound (1h) was identified as a hit candidate exhibiting MIC of 0.04⯵gâ¯mL-1, closer to the MIC value of Isoniazid (0.02⯵gâ¯mL-1), a commercially available drug for the treatment of tuberculosis. Compound 1h also displayed a low level of toxicity in Vero cells along with a good safety profile in vitro. Compounds that showed potent anti-tubercular activity were also found to cleave DNA more efficiently and thereby exhibit nuclease activity. The most active compound (1h) was further studied to deduce the mode of interaction with model serum protein, bovine serum albumin (BSA).
Asunto(s)
Antituberculosos/farmacología , Cumarinas/farmacología , Éteres/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Oximas/farmacología , Albúmina Sérica Bovina/química , Animales , Antituberculosos/síntesis química , Antituberculosos/química , Bovinos , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Cumarinas/química , División del ADN , Relación Dosis-Respuesta a Droga , Éteres/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oximas/química , Relación Estructura-Actividad , Células VeroRESUMEN
Air and moisture stable coordination compounds of late first row transition metals, viz. Co(II), Ni(II), Cu(II) and Zn(II), with a newly designed ligand, 2-(2-benzo[d]thiazol-2-yl)hydrazono)propan-1-ol (LH), were prepared and successfully characterized using various spectro-analytical techniques. The molecular structures of the ligand and nickel complex were unambiguously determined by single-crystal X-ray diffraction method. The [Ni(LH)2]Cl2.3H2O complex is stabilized by intermolecular CHâ¯π stacking interactions between the methyl hydrogen and the C18 atom of the phenyl ring (C11-H11Bâ¯C18) forming 1D zig-zag chain structure. Both, the ligand and its copper complex, were electrochemically active in the working potential range, showing quasi-reversible redox system. The interactions of all the compounds with calf thymus DNA have been comprehensively investigated using electronic absorption spectroscopy, viscosity, electrochemistry and thermal denaturation studies. The cleavage reaction on pBR322 DNA has been monitored by agarose gel electrophoresis. The results showed that the ligand can bind to CT-DNA through partial intercalation, whereas the complexes bind electrostatically. Further, [Ni(LH)2]Cl2.3H2O and [CuLCl(H2O)2] complexes in the series have high binding and cleavage affinity towards pBR322 DNA. Additionally, all the compounds were screened for anti-tuberculosis activity. All the complexes revealed an MIC value of 0.8 µg/mL, which is almost 8 times active than standard used (Streptomycin, 6.25 µg/mL).
Asunto(s)
Antituberculosos/síntesis química , Antituberculosos/farmacología , Benzotiazoles/química , Complejos de Coordinación/farmacología , ADN/química , Elementos de Transición/química , Animales , Antituberculosos/química , Sitios de Unión , Bovinos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , División del ADN , Modelos Moleculares , Estructura Molecular , Plásmidos , Relación Estructura-ActividadRESUMEN
A series of novel Co(II), Ni(II), Cu(II) and Zn(II) complexes of tri and tetratopic hydrazones have been prepared. Ligands L(1)H(2) and L(2)H(2) were synthesized by the condensation of 2-formylphenoxyacetic acid with 2-hydrazinobenzothiazole and 2-hydroxy-3-hydrazinebenzopyrazine, respectively. The prepared complexes were characterized by the analytical and spectral techniques. All the complexes were found to be monomeric in nature with octahedral geometry. Both ligands were found to be electrochemically active in the working potential range showing single electron transfer process attributed to the deprotonation of carboxylic group of the 2-formylphenoxyacetic acid. The potency of the ligand and its complexes as antimicrobial agents has been investigated and made to interact with Escherichia coli DNA to investigate the binding/cleaving ability by absorption, hydrodynamic and electrophoresis studies.