RESUMO
Considering that some thiopyrimidines were previously reported as potential therapeutics, the present study achieved novel analogs of bioactive 2-substituted thiopyrimidines-4-(3H)-ones via base catalyzed alkylation reaction of 2-thiouracil using alkyl and aralkyl bromides. The title compounds were 2-(1-butylthio)pyrimidine-4(3H)-one (5a), 2-(2-butylthio)pyrimidine-4(3H)-one (5b), 2-(cyclohexylmethylthio)pyrimidine-4(3H)-one (5c), 2-(benzylthio)pyrimidine-4(3H)-one (5d) and 2-(1-adamantylthio)pyrimidine-4(3H)-one (5e). Bioactivity tests revealed that thiopyrimidines 5a, 5c, 5d and 5e exhibited antimicrobial activity. The thiopyrimidine-4-one (5c) showed complete inhibition against Streptococcus pyogenes and Branhamella catarrhalis as well as antifungal action against Candida albicans. Significantly, the 1-adamantylthiopyrimidine (5e) was shown to be the most potent cytotoxic compound against multidrug-resistant small cell lung cancer (H69AR). Their structure-activity relationships were discussed.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Pirimidinonas/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antimaláricos/síntese química , Antimaláricos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Moraxella catarrhalis/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Pirimidinonas/síntese química , Pirimidinonas/química , Estereoisomerismo , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
This study investigated bioactive extracts of Polyalthia debilis (Annonaceae) with antimicrobial, antimalarial and cytotoxic activities. Extensive chromatographic isolations provided azafluorenone alkaloids; onychine (1) and 7-methoxyonychine (2) together with a mixture of beta-sitosterol and stigmasterol. The two alkaloids were isolated from the P. debilis for the first time. Isolated fractions containing a mixture of triterpenoids (C7, C8 and C9) exhibited the most potent antimicrobial activity against many bacterial strains with minimum inhibitory concentration of 64 microg/mL. Fractions with antimalarial and cytotoxic activities were also observed. The findings suggest the potential use of P. debilis in medicinal applications.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polyalthia/química , Alcaloides/efeitos adversos , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antimaláricos/efeitos adversos , Antimaláricos/química , Antimaláricos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flavanonas/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Piridonas/química , Sitosteroides/química , Estigmasterol/química , Triterpenos/químicaRESUMO
Bioassay-guided fractionation of the extract of the endophytic fungus KLAR 5 belonging to order Hypocreales, which was isolated from the twig of Knema laurina (Blume) Warb., resulted in the isolation of brefeldin A (1), 8-deoxy-trichothecin (2), trichothecolone (3), 7alpha-hydroxytrichodermol (4), and 7alpha-hydroxyscirpene (5). Compound 5 was isolated from natural source for the first time. Compound 1 was very highly active against human epidermoid carcinoma of the mouth, human breast cancer (BC-1), and human small cell lung cancer (NCI-H187) cells whereas compounds 2 and 4 were selectively active against BC-1 and NCI-H187 cells. Compounds 3 and 5 were moderately active against these three cancer cell lines.
Assuntos
Antineoplásicos/farmacologia , Hypocreales , Myristicaceae/microbiologia , Tricotecenos/farmacologia , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Tricotecenos/isolamento & purificaçãoRESUMO
Eight new compounds (2-9), together with a known dithiodiketopiperazine (1), were isolated from the seed fungus Menisporopsis theobromae BCC 3975. The structures of these substances were elucidated by analyses of spectroscopic data. Compounds 1 and 4 exhibited moderate cytotoxicity against BC-1 cell lines with IC50 values of 29.2 and 57.4 microM, respectively. Cytotoxicity of 1, 2, 4, and 9 against the NCI-H187 cell line showed respective IC50 values of 22.9, 20.3, 1.8, and 56.6 microM. Compounds 2 and 4 exhibited antimalarial activity with IC50 values of 2.95 and 28.8 microM, respectively. Substances 1, 4, 7, 8, and 9 possessed weak antimycobacterial activity (MIC 154.8-952.3 microM), while compounds 2 and 3 showed potent antimycobacterial activity with respective MIC values of 1.24 and 7.14 microM.
Assuntos
Antibacterianos , Antimaláricos , Fungos/química , Piperazinas , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Piperazinas/química , Piperazinas/isolamento & purificação , Piperazinas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , TailândiaRESUMO
An antimalarial macrocyclic polylactone, menisporopsin A (1), was isolated from a cell extract of the seed fungus Menisporopsis theobromae. The structure of 1 was elucidated on the basis of spectroscopic analysis and chemical transformations, with the absolute configuration established by application of the modified Mosher method and by using chiral HPLC. Menisporopsin A (1) possesses an unprecedented residue, 2,4-dihydroxy-6-(2,4-dihydroxy-n-pentyl)benzoic acid. This compound exhibited antimalarial activity, with an IC(50) value of 4.0 microg mL(-1), and antimycobacterial activity (MIC value of 50 microg mL(-1)).
