There is a synergistic interaction between medicinal chemistry, chemoinformatics, and bioinformatics. The last one includes analyses of sequences as well as structural analysis which employ computational techniques such as docking studies and molecular dynamics (MD) simulations. Over the last years these techniques have allowed the development of new accurate computational tools for drug design. As a result, there have been an increased number of publications where computational methods such as pharmacophore modeling, de novo drug design, evaluation of physicochemical properties, and analysis of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties have been quite useful for eliminating the compounds with poor physicochemical or toxicological properties. Furthermore, using MD simulations and docking analysis, it is possible to estimate the binding energy of the protein-ligand complexes by using scoring functions, as well as to structurally depict the binding pose of the compounds on proteins, in order to select the best evaluated compounds for subsequent synthetizing and evaluation through biological assays. In this work, we describe some computational tools that have been used for structure-based drug design of new compounds that target histone deacetylases (HDACs), which are known to be potential targets in cancer and parasitic diseases.
This is a preview of subscription content, log in to check access.
Springer Nature is developing a new tool to find and evaluate Protocols. Learn more
This work was supported by CONACYT Mexico (CB-254600 and PDCPN-782), SIP20160204, COFAA-SIP/IPN COFAASIP/IPN and Centro de Nanociencias y Micro y Nanotecnologías del IPN, México, and CYTED: 214RT0482.
Blundell TL, Abell C, Cleasby A et al (2002) High-throughput X-ray crystallography for drug discovery. In: Flower DR (ed) Drug design: special publication. Royal Society of Chemistry, CambridgeGoogle Scholar
Charifson PS, Kuntz ID (1997) Recent successes and continuing limitations in computer aided drug design. In: Charifson PS (ed) Practical application of computer aided drug design. Dekker, New YorkGoogle Scholar
Rodríguez-Fonseca RA, Sixto-López Y, Fragoso-Vázquez MJ et al (2017) Design, synthesis and biological evaluation of a phenyl butyric acid derivative, N-(4-chlorophenyl)-4-phenylbutanamide: a HDAC6 inhibitor with anti-proliferative activity on cervix cancer and leukemia cell. Anticancer Agents Med Chem 17(10):1441–1454. https://doi.org/10.2174/1871520617666170103092851CrossRefGoogle Scholar
Prestegui-Martel B, Bermúdez-Lugo JA, Chávez-Blanco A et al (2016) N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed in silico with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells. J Enzyme Inhib Med Chem 31(sup3):140–149. https://doi.org/10.1080/14756366.2016.1210138CrossRefGoogle Scholar
1.Laboratorio de Modelado Molecular, Bioinformática y Diseño de Fármacos, de la Escuela Superior de MedicinaInstituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Delegación Miguel Hidalgo, C.P.Ciudad de MéxicoMexico