RESUMEN
This paper describes the synthesis of some novel sulfones having biologically active hydrazides (4-9, 22, 23, 26 and 27), hydrazonoyl cyanide (24), 1,2-dihydropyridines (16-21), chromene (28) and benzochromene (29) moieties starting with 1-[4-(piperidin-1-ylsulfonyl)phenyl]-ethanone 1. The structures of the the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR and 13C NMR. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF7).
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Benzopiranos/síntesis química , Benzopiranos/farmacología , Dihidropiridinas/síntesis química , Dihidropiridinas/farmacología , Hidrazinas/síntesis química , Hidrazinas/farmacología , Sulfonas/síntesis química , Sulfonas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Espectrofotometría Infrarroja , Relación Estructura-ActividadRESUMEN
A variety of novel 1,2-dihydropyridines 10-17, thiophenes 18-21 and thiazole 22 having a biologically active sulfone moiety were obtained via the reaction of 2-cyano-N'-[1-(4-(piperidin-1-ylsulfonyl) phenyl) ethylidene] acetohydrazide 3 with a variety of reagents. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in-vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 15 and 11 with IC(50) values (20.6, 25.5 µM) exhibited better activity than Doxorubicin as a reference drug with IC(50) value (32.02 µM), while compound 14 is nearly as active as Doxorubicin as positive control.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Dihidropiridinas/química , Dihidropiridinas/farmacología , Dihidropiridinas/uso terapéutico , Humanos , Concentración 50 Inhibidora , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/farmacología , Tiazoles/uso terapéutico , Tiofenos/química , Tiofenos/farmacología , Tiofenos/uso terapéuticoRESUMEN
In present investigation a series of 28 oxadiazole analogues (AB1-AB28) were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) & MolSoft (MolSoft, 2007) softwares, lipophilicity and solubility parameters using ALOGPS 2.1 program. Out of 28 analogues only 16 were chosen on the basis of Lipinski "Rule of Five" (Ro5) for the synthesis and antimicrobial screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (1.22) was found to be of compound AB13. Selected compounds (AB1-AB2), (AB5-AB9), (AB12-AB16), (AB18-AB21) were synthesized and characterized by IR, NMR and mass spectral analysis followed by antibacterial and antifungal screening. It was observed that compounds showed moderate to good antibacterial activity, but their antifungal activity was somewhat moderate. Compounds AB13 and AB20 showed pronounced activity against all bacterial and fungal strains. We had noticed that compounds (AB13, AB20) bearing OH group at one of the phenyl ring of oxadiazole exhibited good antimicrobial properties and their drug-likeness model score were also predicted maximum among the series.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Oxadiazoles/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oxadiazoles/síntesis química , Oxadiazoles/química , Solubilidad , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
It has been reported that aryl/heteroaryl sulfonamide compounds may act as anticancer agents through a variety of mechanisms and the most prominent of these mechanisms is through the inhibition of carbonic anhydrase isozymes. The present work reports the possible utility of 4-(cyclohexenylamino)benzenesulfonamide in the synthesis of some novel 4-(quinolin-1-yl)benzenesulfonamide derivatives 6a-u. The structures of these compounds were confirmed by elemental analyses, IR, (1)H NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Some compounds showed interesting in vitro anticancer activities when compared with doxorubicin as a reference drug. In addition, docking of the synthesized compounds into carbonic anhydrase isozyme II (CA II) active site was performed in order to give a suggestion about the proposed mechanism of action.