RESUMEN
Nicotinamide, known as Vitamin-B3, has shown promising potential in improving various medical conditions. Carbacylamidophosphates (CAPh) are versatile phosphoramide ligands with a wide range of applications in both biochemistry and chemistry. Herein, to obtain compounds with enhanced anticancer activity and study the effect of the structure on this activity, four new Co(II) complexes of vitaminB3-based CAPh ligands with the formula of CoCl2[3-NC5H4CONHPO(NC5H10)2]2(C1), CoCl2[3-NC5H4CONHPO(NC5H9CH3)2]2(C2), CoCl2[3-NC5H4CONHPO(NC6H12)2]2(C3), and CoCl2[3-NC5H4CONHPO(NC4H10)2]2(C4) were designed and synthesized. FT-IR, UV-Vis, Atomic Absorption (AAS),1H, 13C, and 31PNMR, and Mass spectroscopies beside CHN and Molar conductivity methods were utilized to characterize the synthesized compounds. Using MTT-assay and Flow Cytometry, the anticancer effects of these complexes were studied on three distinct cell lines, including one normal cell line (MCF10A) and two cancer cell lines (MDA-MB-231, MCF-7). Results showed that our ligands could form complexes by coordinating with cobalt, which, not only have a very strong killing effect on cancer cells but also have a higher level of safety for normal cells and are more cost-efficient than Cisplatin. C3 was the most effective complex at inhibiting the growth of MCF-7 and MDA-MB-231 cells which exhibited a remarkable 97.5 % reduction in cancer cell growth and a Selectivity Index up to > 37. This is an impressive 93 and 54 times more selective and safer than commonly used drugs like Cisplatin and Doxorubicin, respectively.Flow Cytometry analysis shows complex-induced breast cancer cell apoptosis.The ligands' amine structure and ring size can directly impact the complexes' anticancer effect and safety for normal cells.
Asunto(s)
Antineoplásicos , Proliferación Celular , Cobalto , Complejos de Coordinación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Amidas/química , Amidas/farmacología , Amidas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cobalto/química , Cobalto/farmacología , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Ligandos , Estructura Molecular , Relación Estructura-Actividad , Niacinamida/química , Niacinamida/farmacologíaRESUMEN
OBJECTIVE: Adolescence is a crucial time for brain maturation. We investigated the protective effects of metformin (Met) on behavioral changes, oxidative stress, tumor necrosis factor alpha (TNF-α) and nitrite in adulthood induced by ethanol (Eth) consumption during adolescent to adult period of rats. MATERIALS AND METHODS: The adolescence male rats (21 days old) were treated as: 1) Control, 2) Eth (Eth in drinking water (20 %)), 3-5) Eth-Met50, 100 and 150 mg/kg (Eth in drinking water and Met (50, 100, or 150 mg/kg). After 5 weeks treatment, Morris water maze (MMW) and passive avoidance (PA) tests were done. RESULTS: The latency in the MWM test was higher and the latency to enter the dark chamber in the PA test was lower in the Eth group than in control. In Eth-Met100 and 150 groups, they were less than the Eth group. Malondialdehyde (MDA) and nitrite concentration in the hippocampus and cortex of the Eth group were higher than the control group. The thiol content and catalase and superoxide dismutase (SOD) activities in hippocampal and cortical tissues of the Eth group reduced compared to the control group. TNF-α was higher in hippocampal tissues of Eth group animals. Met reversed all of these effects. CONCLUSION: Our findings showed that the protective effects of Met against chronic Eth consumption induced learning and memory impairment were accompanied by decreasing of TNF-a, nitrite and oxidative stress in adolescent rats.
Asunto(s)
Trastornos de la Memoria/tratamiento farmacológico , Metformina/farmacología , Factores de Edad , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/metabolismo , Animales , Encéfalo/metabolismo , Etanol/farmacología , Hipocampo/metabolismo , Masculino , Memoria/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/fisiopatología , Metformina/metabolismo , Enfermedades Neuroinflamatorias/fisiopatología , Nitritos/análisis , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Maduración Sexual/efectos de los fármacos , Maduración Sexual/fisiología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVE: We examined the effectiveness of Hyssopus officinalis (hyssop) aqueous extract on pentylenetetrazole (PTZ)-induced acute seizures and the hippocampus iNOS (inducible nitric oxide synthases) gene expression as a potential mediator of the effects. MATERIALS AND METHODS: Adult male Wistar rats were used. Tonic-clonic seizures were induced by intraperitoneal (i.p.) injection of PTZ (80 mg/kg) then behavioral profile during 30 min was characterized by stages defined as seizure scores. Hyssop extract were prepared and injected (i.p.) 15 minutes before the seizure induction at three doses 50, 100 and 200 mg/kg. Experimental groups were as below: (1) saline+PTZ (n=5); (2) Hyssop 50mg/kg+PTZ (n=10); (3) Hyssop 100mg/kg+PTZ (n=10); (4) Hyssop 200 mg/kg+PTZ (n=8). Two hours after the experimental procedure, all animals were decapitated, brain was removed and right hippocampus was quickly dissected. After total RNA extraction and cDNA synthesis quantitative PCR were used for gene expression of iNOS. RESULTS: Our results showed significant increase (p<0.05) in latency to reach stages 5 and 6 of tonic-clonic seizure at dose 100 mg/kg hyssop extract. In addition, this dose caused significant increase in the gene expression of iNOS in the hippocampus. CONCLUSION: It seems a 100 mg/kg dose of hyssop extract might have anticonvulsant effects. However, these anticonvulsant effects might not occur through the iNOS gene expression.