Synthesis, Cytotoxic Activity and In Silico Study of Novel Dihydropyridine Carboxylic Acids Derivatives
Por:
Ballinas-Indili, Ricardo, Nicolas-Vazquez, Maria Ines, Martinez, Joel, Ramirez-Apan, Maria Teresa, Alvarez-Toledano, Cecilio, Toscano, Alfredo, Hernandez-Rodriguez, Maricarmen, Mera Jiménez E., Miranda Ruvalcaba, Rene
Publicada:
1 oct 2023
Resumen:
To aid the possible prevention of multidrug resistance in tumors and
cause lower toxicity, a set of sixteen novel dihydropyridine carboxylic
acids derivatives 3a-p were produced; thus, the activation of various
ynones with triflic anhydride was performed, involving a nucleophilic
addition of several bis(trimethylsilyl) ketene acetals, achieving good
yields requiring easy workup. The target molecules were unequivocally
characterized by common spectroscopic methods. In addition, two of the
tested compounds (3a, and 3b) were selected to perform in silico studies
due to the highest cytotoxic activity towards the HCT-15 cell line (7.94
+/- 1.6 mu M and 9.24 +/- 0.9 mu M, respectively). Employing theoretical
calculations with density functional theory (DFT) using the
B3LYP/6-311++G(d,p) showed that the molecular parameters correlate
adequately with the experimental results. In contrast, predictions
employing Osiris Property Explorer showed that compounds 3a and 3b
present physicochemical characteristics that would likely make it an
orally active drug. Moreover, the performance of Docking studies with
proteins related to the apoptosis pathway allowed a proposal of which
compounds could interact with PARP-1 protein. Pondering the obtained
results (synthesis, in silico, and cytotoxic activity) of the target
compounds, they can be judged as suitable antineoplastic agent
candidates.
Filiaciones:
Ballinas-Indili, Ricardo:
Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli, 54740, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan Campo 1, Dept Ciencias Quim, Ave 1o Mayo S-N, Cuautitlan 54740, Mexico
Nicolas-Vazquez, Maria Ines:
Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli, 54740, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan Campo 1, Dept Ciencias Quim, Ave 1o Mayo S-N, Cuautitlan 54740, Mexico
Martinez, Joel:
Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli, 54740, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan Campo 1, Dept Ciencias Quim, Ave 1o Mayo S-N, Cuautitlan 54740, Mexico
Ramirez-Apan, Maria Teresa:
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Quim, Circuito Exterior S-N,Ciudad Univ, Mexico City 04510, Mexico
Alvarez-Toledano, Cecilio:
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Quim, Circuito Exterior S-N,Ciudad Univ, Mexico City 04510, Mexico
Toscano, Alfredo:
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Quim, Circuito Exterior S-N,Ciudad Univ, Mexico City 04510, Mexico
Hernandez-Rodriguez, Maricarmen:
Laboratorio de Cultivo Celular, Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, 11340, Mexico
Inst Politecn Nacl, Secc Posgrad Invest, Escuela Super Med, Lab Cult Celular, Mexico City 11340, Mexico
Mera Jiménez E.:
Laboratorio de Cultivo Celular, Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, 11340, Mexico
Miranda Ruvalcaba, Rene:
Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli, 54740, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan Campo 1, Dept Ciencias Quim, Ave 1o Mayo S-N, Cuautitlan 54740, Mexico
gold, Gold
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