RESUMEN
A new series of sulfonylcycloureas derivatives have been synthesized and evaluated in vitro for their antitumor activity against four cancer cell lines (A431, Jurkat, U266, and K562). These compounds were prepared by the condensation of several sulfonamides (2a-m) with ethyl bis(2-chloroethyl)carbamate (1a). The relative cytotoxicity of these new derivatives in comparison to chlorambucil is reported.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Mecloretamina/química , Ureasa/síntesis química , Ureasa/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Relación Estructura-Actividad , Ureasa/químicaRESUMEN
AIM OF THE STUDY: Renal protection and antiurolithiasic effects of two extracts of Paronychia argentea (PA), a traditional Algerian plant commonly known as Algerian tea, were evaluated. This study was carried out to determine whether the aqueous extract (APA) or the butanolic extract (BPA) of aerial parts could prevent or reduce calculi aggregation in experimental calcium oxalate (Ox) nephrolithiasis in Wistar rats. MATERIALS AND METHODS: The two extracts (APA and BPA) were administrated orally and daily, during 28 days to nephrolithiasic treated rats at the dose of 250, 500 mg/kg b.w. and 10, 20mg/kg b.w. respectively. Body weight, renal index, liver index, serum level of creatinine, uric acid, urea, K(+), Ca(2+), Mg(2+), Na(+) and transaminase (alanine aminotransferase, ALT; aspartate aminotransferase, AST), phosphatase alkaline activity (PAL) were evaluated following the 28 days treatment in rats. In addition histopathological changes in kidney and liver were stained in hematoxylin eosin (HE). RESULTS: The effect of the extracts could be advantageous in preventing urinary stone retention by reducing renal necrosis and thus inhibit crystal retention. In contradiction with APA, the two doses of BPA attenuated elevation in the serum creatinine (p<0.01) and blood urea levels (p<0.01) (nephroprotective effect). However, the increase in ALT (27%) and PAL (31-51%) serum levels and in the relative liver weights (p<0.01) in the groups treated with doses of APA may indicate that this extract has not a hepatoprotective effect against oxalate toxicity. CONCLUSIONS: The presented data indicate that administration of the butanolic extract of aerial parts to rats with NaOx induced lithiasis, and reduced and prevented the growth of urinary stones in experimental calcium oxalate nephrolithiasis in Wistar rats.
Asunto(s)
Oxalato de Calcio/metabolismo , Caryophyllaceae , Riñón/patología , Nefrolitiasis/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Creatinina/sangre , Modelos Animales de Enfermedad , Riñón/efectos de los fármacos , Riñón/metabolismo , Cálculos Renales/prevención & control , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Necrosis/prevención & control , Nefrolitiasis/inducido químicamente , Nefrolitiasis/patología , Tamaño de los Órganos/efectos de los fármacos , Oxalatos , Componentes Aéreos de las Plantas , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Urea/sangreRESUMEN
A new series of alkylating agents, 2-chloroethylnitrososulfamides (CENS), were developed on the model of 2-chloroethylnitrosoureas. Starting from chlorosulfonyl isocyanate, a four-step synthesis (carbamoylation-sulfamoylation, Mitsunobu alkylation, deprotection, and nitrosation) gives the title compounds in a 47-58% overall yield. The selection of the nitrosation site can be directed through an alternative route. The pharmacological evaluation shows a significant oncostatic activity towards both A549 and MCF7 cell lines.