We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Synthesis, Cytotoxic Activity and In Silico Study of Novel Dihydropyridine Carboxylic Acids Derivatives.
- Authors
Ballinas-Indilí, Ricardo; Nicolás-Vázquez, María Inés; Martínez, Joel; Ramírez-Apan, María Teresa; Álvarez-Toledano, Cecilio; Toscano, Alfredo; Hernández-Rodríguez, Maricarmen; Mera Jiménez, Elvia; Miranda Ruvalcaba, René
- Abstract
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 μM and 9.24 ± 0.9 μM, 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.
- Subjects
CARBOXYLIC acid derivatives; CARBOXYLIC acids; DIHYDROPYRIDINE; SIGNAL recognition particle receptor; DENSITY functional theory; MULTIDRUG resistance; ANTINEOPLASTIC agents
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 20, p15414
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms242015414