Free 2-propen-1-amine derivative and inclusion complexes with beta-cyclodextrin: scanning electron microscopy, dissolution, cytotoxicity and antimycobacterial activity

Abstract

proporções molares de 1:1 e 1:2 foram analisados por microscopia eletrônica de varredura (SEM). O perfil de dissolução do BBAP e dos complexos de inclusões foram também avaliados durante 6 horas. Por microscopia eletrônica de varredura foi possível observar os complexos de inclusões formados entre BBAP e β-CD por co-evaporação nas proporções molares de 1:1 e 1:2. Como previamente detectado pela caracterização físico-química, na mistura física não se observou a presença de complexo de inclusão. Os estudos de dissolução mostraram que os complexos de inclusões 1:1 e 1:2 liberaram, respectivamente 49.07 ± 1.48 e 40.26 ± 3.90% de BBAP durante 6 horas. BBAP na forma livre foi menos solúvel que os complexos de inclusões e atingiu 9.00 ± 0.75% de dissolução. Os ensaios de citotoxicidade em macrófagos J774 e em uma linhagem de células fibroblásticas de pulmão (V79) indicaram que o BBAP não exibiu efeito tóxico adicional quando complexado com β-CD. Entretanto, os complexos de inclusões foram menos tóxicos para células V79 que BBAP na forma livre. Os complexos de inclusões BBAP/β-CD foram mais efetivos (CIM) que o composto livre em várias cepas de micobactérias. Resultados semelhantes foram observados sobre M. tuberculosis H37Rv intracelular para os complexos de inclusões BBAP/β-CD e rifampicina, uma droga antituberculose de primeira linha.Inclusion complexes and physical mixtures of isomeric mixture of E/Z (50:50) of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N-dimethyl-2-propen-1-amine (BBAP) and β-cyclodextrin (β-CD) in the molar proportion of 1:1 and 1:2 were analyzed by scanning electron microscopy. The dissolution behavior of BBAP and of the inclusion complexes were also evaluated for six hours. By scanning electron microscopy (SEM), it was possible to observe an inclusion complex formed between BBAP and β-CD by co-evaporation, either in the molar proportion of 1:1 or 1:2. In the physical mixtures, no complex was observed as previously detected by physicochemical analysis. The dissolution studies showed that the inclusion complexes BBAP/β-CD 1:1 and 1:2 released respectively 49.07 ± 1.48 and 40.26 ± 3.90% of BBAP during six hours. Free BBAP was less soluble than the inclusion complex and reached 9.00 ± 0.75% of dissolution. Biological assays, such as cytotoxicity to J774 macrophages and to a permanent lung fibroblast cell line (V79), indicated that the BBAP does not exhibit any additional toxic effect with the β-CD complexes. However, the complexes were less cytotoxic to V79 cells than the free form. The BBAP/β-CD inclusion complexes were more effective (MIC) than the free compound on several mycobacteria strains. Similar behavior was observed for BBAP/β-CD complexes and rifampicin, a front-line antitubercular drug, on M. tuberculosis H37Rv growing inside J774 macrophages.

Antimycobacterial Brominated Metabolites from Two Species of Marine Sponges

“…The cytotoxicity effect was assayed on J774 macrophages by the reduction of 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) [14], [15]. Stock solutions of compounds 1 and 2 were prepared in DMSO and diluted in RPMI 1640 medium without phenol red.…”

Study of benznidazole–cyclodextrin inclusion complexes, cytotoxicity and trypanocidal activity

“…8). As found by some authors [19,20] in the case of other drugs, the The lower cytotoxicity against macrophages of BNZ:RM-b-CD could be explained by the differences in solubility between the complexes that are more hydrophilic than the pure drug form. These data show that there is a direct relation between cell toxicity and lipophilicity.…”

“…These data show that there is a direct relation between cell toxicity and lipophilicity. It has frequently been reported in the literature that lipophilic substances tend to possess stronger cytotoxic properties than hydrophilic compounds, owing to the high degree penetration of these molecules into cell membranes [20].…”

Voriconazole–Cyclodextrin Supramolecular Ternary Complex-Loaded Ocular Films for Management of Fungal Keratitis

“…According to literature reports, there exists a direct relationship between the cytotoxicity and lipophilicity of the drug molecules. Lipophilic drugs often possess stronger cytotoxic properties than hydrophilic molecules due to their high degree of penetration into the lipophilic membrane …”

“…Lipophilic drugs often possess stronger cytotoxic properties than hydrophilic molecules due to their high degree of penetration into the lipophilic membrane. 58 3.7.5. HET-CAM Assay.…”