Evaluation of the immunomodulatory effect against splenocytes of Balb/c mice of biflorin obtained from Capraria biflora by a new isolation method

Abstract Biflorin (6,9-dimethyl-3-(4-methylpent-3-en-1-yl) benzo[de]chromene-7,8-dione) is a promising substance that has been increasingly studied in the past decades due to its diverse pharmacological properties (i.e. antitumor, antioxidant, antiinflamatory, antimicrobial activity etc.). Aiming the comprehension of its antitumoral activity we investigated the cell proliferation and cytotoxicity habilities of biflorin against mice splenocytes Balb/c. Biflorin was able to stimulate mice splenocytes Balb/c in 48 h of incubation at a concentration of 20.2 µM. Its immunostimulation promoted the production of cytokines such as: TNF-α, IFN-γ, IL-2, IL-6 and IL-17, inducing the immune profile toward a Th1 response. Moreover, an original method which led to an excellent yield with less processing time compared to the methods described in the literature was developed to obtain biflorin, from sawdust of Capraria biflora L., Scrophulariaceae. This method shows a great potential of increasing the production of this pharmacological active compound.

Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles.

In this work we reported the synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities in vitro of three new compound series obtained from ethyl(5-methyl-1-H-imidazole-4-carboxylate): acylthiosemicarbazide analogues 3a-d, 4-thiazolidinone analogues 4a-d and 1,3,4-thiadiazole analogues 5a-d. All synthesized compounds were characterized by IR, (1)H, (13)C NMR and HRMS. The majority of the tested compounds show excellent anti-T. gondii activity when compared to hydroxyurea and sulfadiazine. In addition it was also shown that most of the compounds in this study have a better performance against intracellular tachyzoites. The results for antimicrobial activity evaluation showed weak antibacterial and antifungal activities for all the tested molecules, when compared with the standard drugs (chloramphenicol and rifampicin for antibacterial activity; nistatin and ketoconazole for antifungal activity).

Synthesis, anti-Toxoplasma gondii and antimicrobial activities of benzaldehyde 4-phenyl-3-thiosemicarbazones and 2-[(phenylmethylene)hydrazono]-4-oxo-3-phenyl-5-thiazolidineacetic acids.

In the present communication, a new series of 2-[(phenylmethylene)hydrazono]-4-oxo-3-phenyl-5-thiazolidineacetic acids (2a-p) have been synthesized. Benzaldehyde 4-phenyl-3-thiosemicarbazones substituted (1a-p) were also obtained and used as intermediate to give the title compounds. All synthesized compounds were characterized by IR, (1)H and (13)C NMR. The in vitro anti-Toxoplasma gondii activity of 1a-p and 2a-p was evaluated. The 4-thiazolidinones (2a-p) were screened for their in vitro antimicrobial activity. For anti-Toxoplasma gondii activity, in general, all compounds promoted decreases in the percentage of infected cells leading to parasite elimination. These effects on intracellular parasites also caused a decrease in the mean number of tachyzoites. In addition, most of the 4-thiazolidinones showed more effective toxicity against intracellular parasites, with IC(50) values ranging from 0.05 to 1 mM. According to results of antimicrobial activity, compounds 2f, 2l, and 2p showed best activity against Mycobacterium luteus, 2c was more active against Mycobacterium tuberculosis, and 2g, 2l, and 2n showed same activity as nistatin (standard drug) against Candida sp. (4249).

Synthesis of thiosemicarbazone and 4-thiazolidinone derivatives and their in vitro anti-Toxoplasma gondii activity.

Thiosemicarbazone and 4-thiazolidinone derivatives were synthesized in one and two step, respectively, from thiosemicarbazide, in satisfactory yields. Then, the synthesized compounds were submitted to evaluation against host cells infected with Toxoplasma gondii. The present studies showed that thiosemicarbazones 2 and 4-thiazolidinone derivatives 3 were effective against intracellular T. gondii.

Desenvolvimento do algoritmo de classificação hierárquica (Winclus) e aplicação à série de derivados indol-2-carboxilato / Development of a Hierarquical Classification Algorithm (Winclus) and its application to a indole-2-carboxylate series

A Classificação Hierárquica ou Cluster Analysis é um tipo de reconhecimento de padrões aplicável ao planejamento de fármacos. Nesse trabalho, apresenta-se um modelo de classificação aglomerativa, de forma a agrupar substituintes com base nas similaridades dos seus parâmetros físico-químicos. Uma vez agrupados, estuda-se a relação entre o modelo de classificação hierárquica e as respostas biológicas dos compostos, a partir da Relação Quantitativa Estrutura-Atividade (QSAR). O método é representado por um novo algoritmo, denominado Winclus, para o qual foi desenvolvido um programa destinado à sua aplicação. Neste trabalho, é abordo o desenvolvimento do software e a aplicação do mesmo à série...