RESUMO
A series of novel 6-methoxy-2-(piperazin-1-yl)-4H-chromen-4-one and 5,7-dimethoxy-2-(piperazin-1-ylmethyl)-4H-chromen-4-one derivatives of biological interest were prepared and screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Among all the compound screened (5a-j and 10k-t), the compounds 5c, 5g, 5h, 10l, 10m, 10n and 10r found to have promising anti-inflammatory activity (up to 65-87% TNF-α and 70-93% IL-6 inhibitory activity) at concentration of 10 µM with reference to standard dexamethasone (71% TNF-a and 84% IL-6 inhibitory activities at 1 µM) while the compounds 5b, 5i, 5j, 10s and 10t found to be potent antimicrobial agent showing even 2 to 2.5-fold more potency than that of standard ciprofloxacin and miconazole at the same MIC value of 10 µg/mL.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Flavonas/química , Flavonas/farmacologia , Anti-Infecciosos/síntese química , Anti-Inflamatórios/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Flavonas/síntese química , Fungos/efeitos dos fármacos , Humanos , Interleucina-6/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Piperazina , Piperazinas/síntese química , Piperazinas/química , Piperazinas/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological interest were prepared by sequential Bigineli's reaction, reduction followed by reaction of resulting amines with different arylisocynates. All the synthesized (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological activity evaluation study reveled that among all the compounds screened, compounds 12 and 17 found to have promising anti-inflammatory activity (68-62% TNF-α and 92-86% IL-6 inhibitory activity at 10 µM). Interestingly compounds 3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10-30 µg/mL against selected pathogenic bacteria and fungi.
Assuntos
Antibacterianos/síntese química , Anti-Inflamatórios/síntese química , Antifúngicos/síntese química , Pirimidinonas/química , Ureia/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Testes de Sensibilidade Microbiana , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Ureia/síntese química , Ureia/farmacologiaRESUMO
A series of novel 1,2,4-oxadiazole, phthalimide, amide and other derivatives of ISO-1 were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds inhibited MIF enzymatic activity at levels better than ISO-1. Of note, compounds 7, 22, 23, 24, 25 and 27 inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells and, more importantly, inhibited the MIF-induced production of interleukin-6 (IL-6) and/or interleukin-1beta (IL-1beta) significantly better than ISO-1.