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•Design arylcarbamate-N-acylhydrazones derivatives were BuChE selective inhibitors.•The compounds were synthesized using low-cost and simple methodologies.•Compounds 10a-d are potent ...BuChE inhibitors, with IC50 values of 0.07–0.56 µM.•Best inhibitor 10c is non-competitive type of BuChE.•Docking studies confirmed important interactions of 10c with hBuChE active site.
A novel series of arylcarbamate-N-acylhydrazones derivatives have been designed and synthesized as potential anti-cholinesterase agents. In vitro studies revealed that these compounds demonstrated selective for butyrylcholinesterase (BuChE) with potent inhibitory activity. The compounds 10a-d, 12b and 12d were the most potent BuChE inhibitors with IC50 values of 0.07–2.07 µM, highlighting the compound 10c (IC50 = 0.07 µM) which showed inhibitory activity 50 times greater than the reference drug donepezil (IC50 = 3.54 µM). The activity data indicates that the position of the carbamate group in the aromatic ring has a greater influence on the inhibitory activity of the derivatives. The enzyme kinetics studies indicate that the compound 10c has a non-competitive inhibition against BuChE with Ki value of 0.097 mM. Molecular modeling studies corroborated the in vitro inhibitory mode of interaction and show that compound 10c is stabilized into hBuChE by strong hydrogen bond interaction with Tyr128, π-π stacking interaction with Trp82 and CH⋯O interactions with His438, Gly121 and Glu197. Based on these data, compound10cwas identified as low-cost promising candidate for a drug prototype for AD treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Pyrimido4,5-dpyridazinone-N-acylhydrazones were synthesized by simple methodologies.•Antifungal activity of compounds was evaluated against P.brasiliensis and Candida spp.•Six ...compounds showed inhibition against Pb18 with MIC of 0.125 to 64 µg.mL−1.•N-acylhydrazone 5a showed potent fungicidal profile with MFC of 0.5 µg mL−1.•Compound 5a showed good synergic effect with amphotericin B and not showed toxicity.
Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido4,5-dpyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL−1. Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL−1, synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Novel 4-methoxy-naphthalene derivatives were synthesized based on
structures in order to evaluate the antifungal activity against
spp.
Antifungal activity of compounds was evaluated against
.
and ...most promising compounds
and
were tested against eight clinically important fungal species.
Compound
was the more active compound with MIC 8 to 32 μg.ml
for
spp without toxicity monkey kidney and murine macrophagecells. Carbohydrazide
showed good synergistic antifungal activity with amphotericin B against
specie. Titration assay of carbohydrazide
with
HSD enzyme demonstrates the binding ligand-protein. Molecular dynamics simulations show that ligand
let the
HSD protein more stable.
New carbohydrazide
is an attractive lead for drug development to treat paracoccidioidomycoses.
1,8-Diazabicyclo5.4.0undec-7-ene (DBU)-based ionic liquids (ILs) has exhibited a high catalytic activity in the aza-Michael reactions compared to conventional catalysts and with imidazole-based ILs. ...In the present work DBU-based ILs showed high catalytic potential for aza-Michael addition of aromatic amines to 2-cyclohexen-1-one under solvent-free condition. Electrospray ionization-mass spectrometry (ESI-MS) and density functional theory studies have been carried out to provide an effective activation mode of DBU-based ILs in aza-Michael addition. Our results show that both the presence of the acid hydrogen in the IL and the ability of the anion to carry out a hydrogen bond with the −NH2 group of the arylamine are fundamental for the reaction catalysis. The catalytic model proposed can be used for the rational development of new ILs with excellent catalytic properties.
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