Abstract
In previous research, a series of cytotoxic anticancer analogues related to 2-acylamino-1,4-naphthoquinone derivatives has been demonstrated. As microtubule plays an important role in many essential cellular processes such as mitosis, tubulin is an important target of anticancer drug. This study performed molecular docking simulation, pharmacophore model, comparative force field analysis model, and comparative similarity indices analysis model to investigate the relationship between inhibitory activities and the properties of compounds, in order to further progress the development of cytotoxic anticancer analogues. These compounds have common H-bond interactions with key residues Lys254 and Lys352, but compounds with large R2 substituent have different docking poses than compounds with small R2 substituent. Some of derivatives such as compound 18 formed the H-bonds with residue Lys254 using the oxygen atoms in R1 substituent and formed π-cation interactions with residue Lys352 using phenyl moiety of 1,4-naphthoquinone. The R1 substituent of these compounds preferred to have disfavored hydrophobic fields and favorable space toward the direction of residue Asn258, while the R2 substituent of these compounds preferred to have about 2-3 carbon chain length hydrophobic substituent toward the direction of residues Ala316 and Lys352. These results offer some beneficial advices for further study in anticancer drug development process.
Highlights
In previous research, it demonstrates a series of cytotoxic anticancer analogues related to 2-acylamino1,4-naphthoquinone derivatives with their inhibitory concentration [1]
As microtubule plays an important role in many essential cellular processes such as mitosis, tubulin is an important target of anticancer drug
This study performed molecular docking simulation, pharmacophore model, comparative force field analysis model, and comparative similarity indices analysis model to investigate the relationship between inhibitory activities and the properties of compounds, in order to further progress the development of cytotoxic anticancer analogues
Summary
It demonstrates a series of cytotoxic anticancer analogues related to 2-acylamino1,4-naphthoquinone derivatives with their inhibitory concentration [1]. Microtubules, which are polymerized by α-tubulins and β-tubulins, are a major component of the cellular cytoskeleton [2, 3] It is a major cellular target of anticancer drug as it plays an important role in many essential cellular processes such as mitosis [4,5,6,7]. A series of cytotoxic anticancer analogues related to 2-acylamino-1,4naphthoquinone derivatives has been demonstrated. As microtubule plays an important role in many essential cellular processes such as mitosis, tubulin is an important target of anticancer drug
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