Synthesis, antineoplastic
activity and in silico studies of (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-tolyl)-1,2,4-oxadiazole-5-carboxamide
Santos Cláudia Laís Araújo Almeida, Santos Jonh Anderson Macêdo, Caiana Rodrigo
Ribeiro Alves, Souza Silvia Maria, Freitas Jucleiton José Rufino, Militão Gardênia
Carmem Gadelha and Freitas Juliano Carlo Rufino
Res. J. Chem. Environ; Vol. 25(7); 167-176;
doi: https://doi.org/10.25303/257rjce16721; (2021)
Abstract
The development of chemotherapy agents without side effects is a major challenge,
since traditional medicines usually have undesirable properties such as high toxicity,
resistance and low bioavailability. In this sense, computational methods play a
crucial role in the discovery and optimization of new drugs, as they combine speed
and efficiency with low cost. The 1,2,4-oxadiazoles are one of the main classes
of heterocyclics due to their numerous biological applications.
In this work, we report the synthesis, antineoplastic evaluation and in silico study
of a new 1,2,4-oxadiazole. The (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-toluyl)-1,2,4-oxadiazole-5-carboxamide
was obtained after two reaction steps in excellent yield. Although it has shown
low activity in relation to the MCF-7, HCT116 and HL60 tumor cell lines, the molecular
docking study indicates that this compound acts in the colchicine site and can inhibit
tubulin polymerization. From the calculation of pharmacokinetic properties by the
SwissADME and Osiris Property Explorer programs, it is possible to infer that the
compound meets the Lipinski rules presenting good oral bioavailability and low toxicity.
