title: Synthesis, biological, and theoretical evaluations of new 1,2,3-triazoles against the hemolytic profile of the Lachesis muta snake venom.
abstract: The current treatment used against envenomation by Lachesis muta venom still presents several side effects. This paper describes the synthesis, pharmacological and theoretical evaluations of new 1-arylsulfonylamino-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid ethyl esters (8a-f) tested against the hemolytic profile of the L. muta snake venom. Their structures were elucidated by one- and two-dimensional NMR techniques ((1)H, APT, HETCOR (1)J(CH) and (n)J(CH), n=2, 3) and high-resolution electrospray ionization mass spectrometry. The series of triazole derivatives significantly neutralized the hemolysis induced by L. muta crude venom presenting a dose-dependent inhibitory profile (IC(50)=30-83 microM) with 1-(4'-chlorophenylsulfonylamino)-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid ethyl ester (8e) being the most potent compound. The theoretical evaluation revealed the correlation of the antiophidian profile with the coefficient distribution and density map of the Highest Occupied Molecular Orbitals (HOMO) of these molecules. The elucidation of this new series may help on designing new and more efficient antiophidian molecules.
authors.affiliation: Departamento de Química Orgânica, Universidade Federal Fluminense, Outeiro de São João Batista, Niterói 24020-141, Rio de Janeiro, Brazil.
authors.forename: Vinícius R
authors.initials: VR
authors.lastname: Campos
authors.forename: Paula A
authors.initials: PA
authors.lastname: Abreu
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Alessandro K
authors.initials: AK
authors.lastname: Jordão
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Maria C B V
authors.initials: MC
authors.lastname: de Souza
authors.forename: Fernanda da C
authors.initials: Fda C
authors.lastname: Santos
authors.forename: Laura A
authors.initials: LA
authors.lastname: Moura
authors.forename: Thaisa S
authors.initials: TS
authors.lastname: Domingos
authors.forename: Carla
authors.initials: C
authors.lastname: Carvalho
authors.forename: Eládio F
authors.initials: EF
authors.lastname: Sanchez
authors.forename: André L
authors.initials: AL
authors.lastname: Fuly
authors.forename: Anna C
authors.initials: AC
authors.lastname: Cunha
mesh_terms: D000818:Animals; D003435:Crotalid Venoms / Q000633:toxicity*; D004952:Esters / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017819:Viperidae / Q000378:metabolism*
chemical_list: D003435:Crotalid Venoms; D004952:Esters; C072644:Lachesis venom; D014230:Triazoles