Abstract: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.… Show more
“…To identify the main binding site of Amaranth and New coccine to HSA, drug-displacement studies were carried out using site probes for site I (phenylbutazone), site II (ibuprofen), and site III (digitoxin) ,, by steady-state fluorescence measurements. The HSA and site probes were in a fixed proportion of 1:1 (1.0 × 10 –5 M), while successive additions of Amaranth or New coccine were made manually, achieving concentrations of 0.15, 0.30, 0.45, 0.59, 0.74, 0.89, 1.03, 1.18, 1.47, 1.75, 2.04, and 2.32 × 10 –5 M in PBS at 310 K.…”
Food processing and storage cause natural food color to diminish, leading to the addition of synthetic dyes by the industry. Unfortunately, these dyes have potential health risks, such as accumulation in blood plasma and interaction with human serum albumin (HSA). To address this issue, the present study utilized spectroscopic techniques and in silico calculations to report the biophysical profile of the HSA:Amaranth and HSA:New coccine interactions. The study showed that the HSA:Dye interaction is spontaneous (ΔG°< 0) and driven by enthalpy (ΔH°≈ −12 kJ mol −1 ) and entropy (ΔS°≈ 0.05 kJ mol −1 K −1 ). These interactions perturb the secondary structure of HSA weak to moderately. Furthermore, the binding of the dyes to HSA is moderate (K SV ≈ 10 4 M −1 ), and the dyes interact with site I. Importantly, this site is the binding region for anticoagulant and anti-inflammatory drugs, such as warfarin, dicoumarol, diflunisal, and naproxen, suggesting that Amaranth and New coccine may negatively impact the pharmacokinetics of these medicines.
“…To identify the main binding site of Amaranth and New coccine to HSA, drug-displacement studies were carried out using site probes for site I (phenylbutazone), site II (ibuprofen), and site III (digitoxin) ,, by steady-state fluorescence measurements. The HSA and site probes were in a fixed proportion of 1:1 (1.0 × 10 –5 M), while successive additions of Amaranth or New coccine were made manually, achieving concentrations of 0.15, 0.30, 0.45, 0.59, 0.74, 0.89, 1.03, 1.18, 1.47, 1.75, 2.04, and 2.32 × 10 –5 M in PBS at 310 K.…”
Food processing and storage cause natural food color to diminish, leading to the addition of synthetic dyes by the industry. Unfortunately, these dyes have potential health risks, such as accumulation in blood plasma and interaction with human serum albumin (HSA). To address this issue, the present study utilized spectroscopic techniques and in silico calculations to report the biophysical profile of the HSA:Amaranth and HSA:New coccine interactions. The study showed that the HSA:Dye interaction is spontaneous (ΔG°< 0) and driven by enthalpy (ΔH°≈ −12 kJ mol −1 ) and entropy (ΔS°≈ 0.05 kJ mol −1 K −1 ). These interactions perturb the secondary structure of HSA weak to moderately. Furthermore, the binding of the dyes to HSA is moderate (K SV ≈ 10 4 M −1 ), and the dyes interact with site I. Importantly, this site is the binding region for anticoagulant and anti-inflammatory drugs, such as warfarin, dicoumarol, diflunisal, and naproxen, suggesting that Amaranth and New coccine may negatively impact the pharmacokinetics of these medicines.
“…The study revealed that S -alkylated-triazoles 216a-c ( Fig. 43 ) exhibited significant trypanocidal profile with IC 50 values 3.18–3.52 and 3.61–4.15 μmol/L against epimastigote and amastigote forms of T. cruzi , respectively, in comparison to lead compound 215 (IC 50 : 18.30 and 8.87 μmol/L against the epimastigote and amastigote forms, respectively) [ 198 ]. Fig.…”
Section: Biological Activities Of 124-triazole Derivativesmentioning
The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.
“…Adverse effects such as rash, diarrhea, headache, hepatotoxicity, and gastrointestinal problems, including several severe problems, are reported for many triazole drugs [ 25 ]. On the other hand, S -Alkyl-1,2,4-triazoles showed toxic effects against T. cruzi with low toxicity to host cells [ 26 ].…”
This study investigates the efficacy of miltefosine, alkylphospholipid, and alkyltriazolederivative compounds against leukemia lineages. The cytotoxic effects and cellular and molecular mechanisms of the compounds were investigated. The inhibitory potential and mechanism of inhibition of cathepsins B and L, molecular docking simulation, molecular dynamics and binding free energy evaluation were performed to determine the interaction of cathepsins and compounds. Among the 21 compounds tested, C9 and C21 mainly showed cytotoxic effects in Jurkat and CCRF-CEM cells, two human acute lymphoblastic leukemia (ALL) lineages. Activation of induced cell death by C9 and C21 with apoptotic and necrosis-like characteristics was observed, including an increase in annexin-V+propidium iodide-, annexin-V+propidium iodide+, cleaved caspase 3 and PARP, cytochrome c release, and nuclear alterations. Bax inhibitor, Z-VAD-FMK, pepstatin, and necrostatin partially reduced cell death, suggesting that involvement of the caspase-dependent and -independent mechanisms is related to cell type. Compounds C9 and C21 inhibited cathepsin L by a noncompetitive mechanism, and cathepsin B by a competitive and noncompetitive mechanism, respectively. Complexes cathepsin-C9 and cathepsin-C21 exhibited significant hydrophobic interactions, water bridges, and hydrogen bonds. In conclusion, alkyltriazoles present cytotoxic activity against acute lymphoblastic lineages and represent a promising scaffold for the development of molecules for this application.
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