New 2-Aryl-1,4-naphthoquinone-1-oxime Methyl Ether Compound Induces Microtubule Depolymerization and Subsequent Apoptosis

Abstract

Abstract. In this study, we describe the antitumor activity of QO-1, one of the new 2-aryl-1,4-naphthoquinone-1-oxime methyl ether derivatives. QO-1 is a derivative of macarpine, a natural occurring product from Rutaceae plant. It could potently inhibit cell growth when tested on 19 cancer cell lines. To investigate its mechanism, two cell lines (HeLa and MCF-7) sensitive to QO-1 were selected. Based on flow cytometry, it was found to induce G 2 /M-phase arrest. Moreover, it could cause microtubule depolymerization both in vitro and in vivo. On the other hand, QO-1 activated spindle assembly checkpoint (SAC) proteins. Expression of Bub1, one of the SAC, was gradually increased, reaching a peak after 16 -20 h, and then gradually decreased. Instead, QO-1 increased the sub-G 1 population, which suggested a cell death population. Actually, expression of Bcl-2 family proteins and activation of caspase-3/7 were evidences of apoptosis. Consistent with these results, cells with DNA fragmentation and multinucleated cells were increased timedependently after QO-1 exposure. In conclusion, QO-1 has promising antitumor effects via microtubule depolymerization.

Synthetic Naphthoquinone Derivatives as Anticancer Agents in Ovarian Cancer: Cytotoxicity Assay and Investigation of Possible Biological Mechanisms Action

“…Regarding the interference of the naphthoquinones 3 and 4 directly in the cell cycle, our results corroborate other authors, who have demonstrated interference in the cell cycle caused by naphthoquinones [28,29] …”

“…Regarding the interference of the naphthoquinones 3 and 4 directly in the cell cycle, our results corroborate other authors, who have demonstrated interference in the cell cycle caused by naphthoquinones. [28,29] Furthermore, the change in the cell cycle caused by 4 it can also be rationalized in terms of interaction (alkylation) with DNA. This naphthoquinone derivative possesses the carbon C 3 of the naphthoquinone core Table 2.…”

Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes

“…This alkaloid and its derivatives also show strong cytotoxic effects in cancer cells. 7 In the case of chelirubine and sanguirubine, antimicrobial, anti-parasitic and anticancer effects have been demonstrated. 8,9 Besides these various biological effects on cells 2, 10 , QBA's in their iminium form were reported to interact with double stranded DNA (dsDNA) with a relatively weak mode 1,11 and comparable to that of ethidium bromide 12 .…”

Synthesis of Methoxy-, Methylenedioxy-, Hydroxy-, and Halo-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors and Their Biological Activity for Drug-Resistant Cancer

“…Molecular modeling shows two hydrogen bonds between the oxygen atoms of the methylenedioxy group of NTD-96, and the residues of TOP1, Thr718 (3.6 Å), and Asn722 (3.7 Å) were observed, implying this methylenedioxy group as playing a key role in the interaction between TOP1 and the inhibitor . Additionally, the position and number of the methoxy or methylenedioxy group affects the biological activity of the natural benzo­[c]­phenanthridine alkaloids, such as sanguinarine, − chelerythrine, , macarpine, fagaridine, , and fagaronine (Figure S1, Supporting Information). , These observations encouraged us to study the effect of the position and number of methoxy and methylenedioxy group as well as the displacement by a hydroxy or halogen group on TOP1 and TDP1 inhibitory activities. Therefore, three series of benzophenanthridinone derivatives were designed.…”