88818-28-4Relevant articles and documents
Synthesis and Evaluation of New Naphthalene and Naphthoquinone Derivatives as Anticancer Agents
Beretta, Giovanni L.,Ribaudo, Giovanni,Menegazzo, Ileana,Supino, Rosanna,Capranico, Giovanni,Zunino, Franco,Zagotto, Giuseppe
, (2017)
DNA topoisomerase I inhibitors, both synthetic and of natural origin, are receiving increasing consideration primarily as drugs against refractory tumors. Alkannin and shikonin, two enantiomeric dyes from Alkanna tinctoria and Lithospermum erythrorhizon, have been known over many centuries as dyestuff, wound healing, anti-inflammatory, antibacterial and antitumor substances. Although multiple mechanisms appear to be implicated, their potency is associated with the inhibition of topoisomerase I and with the redox properties of the naphthazarin scaffold. Here, the synthesis of new naphthalene and naphthoquinone derivatives inspired by alkannin and shikonin is described and their structural and biological properties were examined. Different oxidation states of the naphthalene nucleus were examined to observe the effect of this parameter on cytotoxicity. Antiproliferative activities against a panel of human cancer cell lines were evaluated and the implication of topoisomerase I was assessed.
Discovery of heterocycle-containing α-naphthoflavone derivatives as water-soluble, highly potent and selective CYP1B1 inhibitors
Dong, Jinyun,Huang, Guang,Cui, Qing,Meng, Qingqing,Li, Shaoshun,Cui, Jiahua
, (2020/10/18)
Cytochrome P450 1B1 (CYP1B1) has been well validated as an attractive target for cancer prevention and drug resistance reversal. In continuation of our interest in this area, herein, a set of forty-six 6,7,10-trimethoxy-α-naphthoflavone derivatives varying in B ring was synthesized and screened against CYP1 enzymes, leading to the identification of fluorine-containing compound 15i as the most potent and selective CYP1B1 inhibitor (IC50 value of 0.07 nM), being 84-fold more potent than that of the template molecule ANF. Alternatively, the amino-substituted derivative 13h not only possessed a potent inhibitory effect on CYP1B1 (IC50 value of 0.98 nM), but also had a substantially increased water solubility as compared with the lead ANF (311 μg/mL for 13h and 5 μg/mL for ANF). The current study expanded the structural diversity of CYP1B1 inhibitors, and compound 13h could be considered as a promising starting point with great potential for further studies.
6-Substituted 1,4-Naphthoquinone Oxime Derivatives (III): Synthesis and Cytotoxic Evaluation
Huang,Liu,Meng,Li
, p. 1025 - 1035 (2018/07/06)
As a continuous study, a set of 23 new 6-substituted 1,4-naphthoquinone oxime derivatives are synthesized and screened for their in vitro cytotoxic activity. Four of those oxime derivatives demonstrate more potent cytotoxic activity towards K562, HCT-15, and HCT-116 cell lines than a reference drug 5-Fu. In particular, compound 21g exhibits the strongest inhibitory activity against K562 cell lines with IC50 values of 1.25 μM. According to flow cytometry data, compound 21g can arrest cell cycle at S phase and induce a strong apoptotic response in K562 cells. The preliminary structure-activity relationship study shows that the nature of substituents in positions 6 and 1' of 1,4-naphthoquinone derivatives significantly affect their cytotoxic activity.
