In this study, we synthesized eight new compounds containing the 2-amino-cycloalkyl[b]thiophene and acridine moieties (ACT and ACS -ACS ). None tested compounds presented human erythrocyte cytotoxicity. The new compounds presented antipromastigote activity, where ACS and ACS derivatives presented significant antileishmanial activity, with better performance than the reference drugs (tri and pentavalent antimonials), with respective IC values of 9.60 ± 3.19 and 10.95 ± 3.96 μm. Additionally, these two derivatives were effective against antimony-resistant Leishmania (Leishmania) amazonensis strains. In addition, binding and fragmentation DNA assays were performed. It was observed that the antileishmanial activity of ACS is not associated with DNA fragmentation of the promastigote forms. However, it interacted with DNA with a binding constant of 10 m . In partial least-squares studies, it was observed that the most active compounds (ACS and ACS ) showed lower values of amphiphilic moment descriptor, but there was a correlation between the lipophilicity of the molecules and antileishmanial activity. Furthermore, the docking molecular studies showed interactions between thiophene-acridine derivatives and the active site of pyruvate kinase enzyme with the major contribution of asparagine 152 residue for the interaction with thiophene moiety. Thus, the results suggested that the new thiophene-acridine derivatives are promising molecules as potential drug candidates.

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Background/Aim: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4chlorobenzylidene)amino)-5 -4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. Materials and Methods: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. Results: AMTAC-06 did not induce toxicity on zebrafish and mice (LD 50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G 1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an antiangiogenic action, possibly dependent on the cytokine modulation . No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. Conclusion: AMTAC-06 has low toxicity and a significant antitumor activity.The mechanisms underlying the transformation of normal cells into malignant cells have been thoroughly studied, aiming to better understand the biology of cancer and develop new treatments. Researchers have described common traits acquired during tumorigenesis, including sustaining proliferative signaling, induction of angiogenesis, deregulation of cell cycle, resistance to cell death and tumorpromoting inflammation (1-3). These hallmarks are important therapeutic targets for new antitumor drug development (3,4).Acridines are heterocyclic molecules containing a planar ring, which have shown anti-inflammatory, anticancer, antiparasitic, antiviral, and antimicrobial activities, among others (5). Their antitumor action is based on DNA binding and topoisomerase inhibition (6), which may cause apoptosis and cell cycle arrest (7). Nevertheless, acridine compounds 5049

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Animais de diferentes criadouros podem apresentar variações em seus parâmetros fisiológicos. Os objetivos desse trabalho foram determinar o intervalo de valores de referência de parâmetros bioquímicos e hematológicos de ratos e ratas Wistar (Rattus norvegicus) da Unidade de Produção Animal do Instituto de Pesquisa em Fármacos e Medicamentos da Universidade Federal da Paraíba (UPA/IPeFarM/UFPB), bem como comparar os dados encontrados com dados publicados para outras unidades de produção animal nacionais e internacionais. Foram utilizados animais saudáveis (n=40/gênero), com 8 a 12 semanas de idade e peso entre 150 e 300 g. Amostras de sangue total foram obtidas por punção intracardíaca e utilizadas para a quantificação de eritrócitos, leucócitos, plaquetas e dos índices hematimétricos. Foram determinadas as concentrações séricas de glicose, triglicérides, colesterol, proteínas totais, ureia, albumina, creatinina, ácido úrico e a atividade enzimática da aspartato aminotransferase, alanina aminotransferase e fosfatase alcalina. Ao comparar os gêneros, foram observadas diferenças significativas entre todos os parâmetros avaliados. Além disso, foram encontradas discrepâncias entre os valores obtidos (exceto proteínas totais, ácido úrico e hemácias) e resultados de outros criadouros. É necessário, portanto, que cada biotério determine os valores de referência do perfil fisiológico de seus animais, considerando os fatores intrínsecos e extrínsecos na homeostase dos mesmos, a fim de fornecer dados reais para os experimentos de suas instituições.