RESUMO
Nootkatone, an approved insecticide, is a well-known natural product from grapefruit. A series of fused-thiazole derivatives of nootkatone have been synthesized, and these new compounds were tested against several strains of bacteria. Some of these compounds are found to be potent antimicrobial agents against Staphylococcus aureus and Enterococcus faecium with minimum inhibitory concentration (MIC) values as low as 1.56â µg/mL. The lead compound is bactericidal and very potent against S.â aureus persisters. These compounds are nontoxic to human cancer cell lines at 10â µm concentration.
Assuntos
Antibacterianos/farmacologia , Enterococcus faecium/efeitos dos fármacos , Sesquiterpenos Policíclicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Tiazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Sesquiterpenos Policíclicos/química , Relação Estrutura-Atividade , Tiazóis/químicaRESUMO
In an effort to synthesize a library of bioactive molecules, we present an efficient synthesis of fused-thiazole derivatives of natural products and approved drugs by using an environmentally usable solvent, acetic acid, and without any external reagent. Cholestenone, ethisterone, progesterone, and nootkatone-derived epoxyketones have been utilized to synthesize 50 novel compounds. The plausible mechanism of the reaction has been determined by theoretical calculation using M06-2X/6-31+G(d,p). These novel molecules have been tested against cancer cell lines and pathogenic bacterial strains. Several ethisterone-based fused-thiazole compounds are found to be potent growth inhibitors of cancer cell lines at submicromolar concentrations.
RESUMO
We report the synthesis and antimicrobial studies of a new series of naphthyl-substituted pyrazole-derived hydrazones. Many of these novel compounds are potent growth inhibitors of several strains of drug-resistant bacteria. These potent compounds have inclined growth inhibitory properties for planktonic Staphylococcus aureus and Acinetobacter baumannii, and its drug-resistant variants with minimum inhibitory concentration (MIC) as low as 0.78 and 1.56 µg ml-1, respectively. These compounds also show potent activity against S. aureus and A. baumannii biofilm formation and eradication properties. Time Kill Assay shows that these compounds are bactericidal for S. aureus and bacteriostatic for A. baumannii. The probable mode of action is the disruption of the bacterial cell membrane. Furthermore, potent compounds are nontoxic to human cell lines at several fold higher concentrations than the MICs.
Assuntos
Desenho de Fármacos , Hidrazonas/síntese química , Staphylococcus aureus/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana , Hidrazonas/farmacologia , Testes de Sensibilidade Microbiana , Naftalenos/síntese química , Naftalenos/farmacologiaRESUMO
In this paper, synthesis and antimicrobial studies of 31 novel coumarin-substituted pyrazole derivatives are reported. Some of these compounds have shown potent activity against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) as low as 3.125 µg/mL. These molecules are equally potent at inhibiting the development of MRSA biofilm and the destruction of preformed biofilm. These results are very significant as MRSA strains have emerged as one of the most menacing pathogens of humans and this bacterium is bypassing HIV in terms of fatality rate.
Assuntos
Cumarínicos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Anti-Infecciosos , Biofilmes/efeitos dos fármacos , Cumarínicos/metabolismo , Cumarínicos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pirazóis/metabolismo , Pirazóis/farmacologia , Infecções Estafilocócicas/microbiologiaRESUMO
Microbial resistance to drugs is an unresolved global concern, which is present in every country. Developing new antibiotics is one of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat bacterial resistance to drugs. Based on our lead molecules, we report the synthesis and antimicrobial studies of 27 new pyrazole derivatives. These new coumarin-pyrazole-hydrazone hybrids are readily synthesized from commercially available starting materials and reagents using benign reaction conditions. All the synthesized molecules were tested against 14 Gram-positive and Gram-negative bacterial strains. Several of these molecules have been found to be potent growth inhibitors of several strains of these tested bacteria with minimum inhibitory concentrations as low as 1.56 µg/mL. Furthermore, active molecules are non-toxic in in vitro and in vivo toxicity studies.