PAMAM-G4 protect the N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) and maintain its antiproliferative effects on MCF-7.

Autor: Ortiz-Morales AA; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico., García-Vázquez JB; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico. benjagv_5202@hotmail.com., Fragoso-Vázquez MJ; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico.; Departamento de Química Orgánica, Escuela Nacional de Ciencias, Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala, Col. Casco de Santo Thomas, Delegación Miguel Hidalgo, 11340, Mexico City, Mexico., Rosales-Hernández MC; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico., Fragoso-Morales LG; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico., Estrada-Pérez AR; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico., Correa-Basurto J; Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation), SEPI-Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, Mexico City, Mexico. corrjose@gmail.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Feb 28; Vol. 13 (1), pp. 3383. Date of Electronic Publication: 2023 Feb 28.
DOI: 10.1038/s41598-023-30144-7
Abstrakt: Our work group designed and synthesized a promissory compound N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA is a HDAC1 inhibitor and antiproliferative in cancer cell lines. However, HO-AAVPA is poor water solubility and enzymatically metabolized. In this work, the fourth-generation poly(amidoamine) dendrimer (PAMAM-G4) was used as a drug deliver carrier of HO-AAVPA. Moreover, HO-AAVPA and HO-AAVPA-PAMAM complex were submitted to forced degradation studies (heat, acid, base, oxidation and sunlight). Also, the HO-AAVPA-PAMAM-G4 complex was assayed as antiproliferative in a breast cancer cell line (MCF-7). The HO-AAVPA-PAMAM-G4 complex was obtained by docking and experimentally using three pH conditions: acid (pH = 3.0), neutral (pH = 7.0) and basic (pH = 9.0) showing that PAMAM-G4 captureand protect the HO-AAVPA from forced degradation, it is due to sunlight yielded a by-product from HO-AAVPA. In addition, the PAMAM-G4 favored the HO-AAVPA water solubility under basic and neutral pH conditions with significant difference (F (2,18)  = 259.9, p < 0.001) between the slopes of the three conditions being the basic condition which solubilizes the greatest amount of HO-AAVPA. Finally, the HO-AAVPA-PAMAM-G4 complex showed better antiproliferative effects on MCF-7 (IC 50  = 75.3 μM) than HO-AAVPA (IC 50  = 192 μM). These results evidence that PAMAM-G4 complex improve the biological effects of HO-AAVPA.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje