Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 µmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.

The interaction between HSA and two semi-synthetic potential anti-cancer agents derived from trans -dehydrocrotonin-methyl-hydrazone (MHDCTN) and phenyl-hydrazone (PHDCTN) was evaluated under physiological conditions at 296, 303 and 310 K by multi-spectroscopic techniques and molecular docking calculations. Steady state fluorescence quenching indicated a ground state association (static quenching) for both samples; however, the quenching induced by PHDCTN was not essentially static and can be accompanied by a dynamic quenching mechanism. The binding is strong (modified Stern-Volmer binding constant (Ka) ca. 105 M-1), causing a very weak perturbation on the secondary structure of the protein and there is just one main binding site for both samples (Sudlow’s site I). Molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces for both samples.

A reatividade fotoquímica do ácido 3-sulfônico da b-lapachona (1) frente a amino ácidos, bases nucleicas ou nucleosídeos foi determinada empregando a técnica de fotólise por pulso de laser de nanossegundo. A excitação (λ = 355 nm) de soluções deaeradas de 1, em acetonitrila, resultou na formação do seu estado excitado triplete, o qual foi suprimido eficientemente por L-triptofano, éster metílico de L-triptofano, L-tirosina, éster metílico de L-tirosina e éster metílico de L-cisteína (k q ≅ 10(9) L mol-1 s-1). Para L-triptofano, L-tirosina e seus ésteres metílicos novos transientes foram formados no proceso de supressão, os quais foram atribuídos ao par de radicais resultante de uma transferência inicial de elétron do amino ácido, ou dos seus ésteres metílicos, à quinona excitada, seguida por uma transferência de próton rápida. Não foi possível a obtenção de constantes de velocidade de supressão para timina e timidina, em acetonitrila, o que pode ser devido tanto ao caráter π π* de 1 quanto ao baixo valor para a sua energia triplete. Por outro lado, a supressão de 1 por 2'-deoxaguanosina foi tão eficiente quanto para triptofano ou tirosina (k q ≅ 10(9) L mol-1 s-1). O rendimento quântico para a formação de oxigênio singlete (¹O2) a partir de 1 foi determinado empregando-se estudos de emissão resolvida no tempo na região do infravermelho próximo, tendo-se obtido um valor consideravelmente alto para este rendimento quântico (ΦΔ= 0,7).

The photochemical reactivity of β-Lapachone-3-sulfonic acid (1) towards amino acids, nucleobases or nucleosides has been examined employing the nanosecond laser flash photolysis technique. Excitation (λ = 355 nm) of degassed solutions of 1, in acetonitrile, resulted in the formation of its corresponding triplet excited state. This transient was efficiently quenched by L-tryptophan, L-tryptophan methyl ester, L-tyrosine, L-tyrosine methyl ester and L-cysteine methyl ester (k q ≅ 10(9) L mol-1 s-1). For L-tryptophan, L-tyrosine and their methyl esters new transients were formed in the quenching process, which were assigned to the corresponding radical pairs resulting from an initial electron transfer from the amino acids, or their esters, to the excited quinone, followed by a fast proton transfer. No measurable quenching rate constants could be observed in the presence of thymine or thymidine, in acetonitrile solution, which is probably due to the π π* character of triplet 1 as well as to its low triplet energy. On the other hand, the rate constant obtained when 1 was quenched by 2'-deoxyguanosine is reasonably fast (k q ≅ 10(9) L mol-1 s-1). The quantum efficiency of singlet oxygen (¹O2) formation from 1 was determined employing time-resolved near-IR emission studies upon laser excitation and showed a considerably high value (ΦΔ= 0.7).

A irradiação na região do ultravioleta de 1,2,3-indanotriona, em presença de 2,3-dimetil-2-buteno, em diclorometano, leva a uma mistura complexa de produtos formados a partir de reações de abstração de hidrogênio, fotocicloadição [2pi+2pi] (reação de Paternò-Büchi) e fotocicloadição [4pi+2pi]. A distribuição de produtos é dependente de fatores eletrônicos e estéricos, com estes últimos sendo os responsáveis pelo alto rendimento químico de formação do produto resultante da cicloadição fotoquímica [4pi+2pi].

UV irradiation of 1,2,3-indanetrione, in CH2Cl2, in the presence of 2,3-dimethyl-2-butene yields a complex mixture of products arising from hydrogen abstraction, [2pi+2pi] photocycloaddition (Paternò-Büchi reaction), and [4pi +2pi] photocycloaddition. The reaction is dependent on electronic and steric effects, with the later accounting for the high chemical yield observed for the formation of the dioxene-type product.