Design, Synthesis, Molecular Modelling and Biological Evaluation of Novel α-Naphtholhydroxamate Derivatives as Potential Anticancer Agents

Abstract

Chemotherapy is one of the treatment options for cancer. A major problem in cancer chemotherapy is the lack of selective toxicity of many commonly used anti-cancer agents towards tumor tissue compared to normal tissue. Studies have shown that α-naphthol is selectively toxic to cultures of human tumor tissue compared to normal tissues in vitro. Hence, this study was conducted to synthesize a series of new hydroxamate derivatives containing α-naphthol nucleus by the reaction of naphthol acetic acid with amino acid methyl ester derivatives which were directly reacted with hydroxyl amine at room temperature. Structures of these compounds were confirmed by standard studies of IR, 1 H NMR, 13 CNMR, MS and elemental analysis. The cytotoxicity of the synthesized compounds were studied using the MTT assay in four human cancer cell lines, including HepG2, PC-3, HT-29 and MCF-7. Among the compounds, compound 6 g and 6 h exhibited a significant cytotoxicity against almost all the used cells including the normal cells . Further studies have shown that the cell death observed was closely associated with generation of reactive oxygen species (ROS). In this study, other naphthol derivatives have shown significant increase in the level of ROS in concentration dependent manner in treated cells. In conclusion, the study has shown that among the synthesized compounds, compounds 6 g , 6 k and 6 h hold the potential for further research. Furthermore, a molecular docking of the tested compounds was carried out to investigate their binding pattern with the prospective target, HDAC (PDB-code: 1T69).

A novel series of substituted 1,2,3‐triazoles as cancer stem cell inhibitors: Synthesis and biological evaluation

“…More so, it is also reported to suppress CSCs in human breast carcinoma cell line MDA‐MB‐231 (Takehara, Hoshino, Namba, Yamakawa, & Mizushima, 2011). In both Series C and D , we incorporated α‐ and β‐naphthol core structures, respectively, based on our earlier findings (Sahu et al, 2019) and the reported literature of naphthol derivatives as anticancer agents (Abdelrahim, Mohan, Albarrati, Makeen, & Safhi, 2016; Das, Reddy, Kashanna, Mamidyala, & Kumar, 2012; Osowole, Kempe, Schobert, & Effenberger, 2011).…”