Substituent effects on the stability, physicochemical properties and chemical reactivity of nitroimidazole derivatives with potential antiparasitic effect: a computational study
Por:
Campos-Fernandez, Linda, Barrientos-Salcedo, Carolina, Herrera Valencia, Edtson E., Ortiz-Muniz, Rocio, Soriano-Correa, Catalina
Publicada:
28 jul 2019
Resumen:
Neglected tropical diseases caused by parasitic pathogens have caused an
increase in research interest in drug discovery. Chagas disease is
caused by protozoan Trypanosoma cruzi. Benznidazole and nifurtimox are
effective drugs in the acute phase; nevertheless, for long-time
treatment, they are toxic and have side effects, because these molecules
produce free radicals and suffer oxidation-reduction processes. Studies
of the structure and mode of action of these drugs have been performed
and, until today, no effective treatment for this disease has been
established yet. DFT-M06-2X studies in solution allowed us to explore
the substituent effects on stability energy, physicochemical properties
and chemical reactivity of nitroimidazoles with potential antiparasitic
effects, using quantum-chemical descriptors: proton affinities,
substituent effect stabilization energy, ionization potential,
electrophilicity, hardness, atomic charges, dipole moment and Fukui
functions. The basicity of the N3 atom and dipole moment decrease while
the ionization potential, electrophilicity, and hardness increase with
the electron-withdrawing substituents. Atomic charges, Fukui functions,
and electrostatic potential showed that the main reactivity was on the
nitro group and N3 atom. The methyl group linked to C2, and the position
and inductive effect caused by the nitro group provoked major changes in
the physicochemical features, chemical reactivity, and geometrical and
energetic stabilities. Quantum-chemical descriptors allowed us to
analyze and design novel nitroimidazole derivatives.
Filiaciones:
Campos-Fernandez, Linda:
Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac, Mexico City 09230, DF, Mexico
UAM, Dept Ciencias Salud, Mexico City 09340, DF, Mexico
UAM, Biol Expt, Mexico City 09340, DF, Mexico
Barrientos-Salcedo, Carolina:
Univ Veracruzana, Fac Bioanal Campus Veracruz, Lab Quim Med & Quimiogenom, Xalapa 91700, Veracruz, Mexico
Herrera Valencia, Edtson E.:
Univ Nacl Autonoma Mexico, FES Zaragoza, Dept Ingn Quim, Mexico City 09230, DF, Mexico
Ortiz-Muniz, Rocio:
UAM, Dept Ciencias Salud, Mexico City 09340, DF, Mexico
Soriano-Correa, Catalina:
Univ Nacl Autonoma Mexico, Fac Estudios Super FES Zaragoza, Unidad Quim Computac, Mexico City 09230, DF, Mexico
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