naphthoquinones and rhinacanthone

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is known as traditional medicine for the treatment of fungal and herpes virus infections. A new naphthoquinone racemate, rhinacasutone (1) together with seven known compounds, rhinacanthone (2), rhinacanthins C, D, N, Q, and E (3-7), and heliobuphthalmin (8) were isolated from root of R. nasutus. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR and MS data. All the isolated compounds were tested for their antiviral activities against PR8, HRV1B, and CVB3-infected vero cells. Compounds 3-6 exhibited significant antiviral activities with the IC

Topics: Acanthaceae; Animals; Antiviral Agents; Benzopyrans; Chlorocebus aethiops; Lignans; Naphthoquinones; Plant Extracts; Plant Roots; Vero Cells

Rhinacanthone, a main bioactive naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical carcinoma (HeLa) cells. beta-Lapachone, an anticancer drug having a chemical structure related to rhinacanthone, was used as a positive control. The results demonstrated that rhinacanthone inhibited proliferation of HeLa cells in a dose-dependent manner and had greater efficacy than that of beta-lapachone: IC(50) values of the compound ranged from 1.2+/-0.1 to 5.5+/-0.86 muM for 2-24 h time periods. Rhinacanthone-treated HeLa cells displayed several apoptotic features as evidenced by the appearance of chromatin condensation, internucleosomal DNA fragmentation, increase in the proportion of sub G(1) apoptotic cells, and externalization of annexin-V. The apoptotic processes by the treatment with rhinacanthone involved in a marked increase in the level of pro-apoptotic protein Bax and decrease in the levels of anti-apoptotic proteins Bcl-2 and survivin as well as subsequent activation of caspase-9 and caspase-3. Moreover, rhinacanthone increased the expression of apoptosis-inducing factor (AIF) which would translocate from mitochondria to nucleus through cytosol, and induce apoptosis through caspase independent signaling pathway. Taken together, our findings for the first time demonstrate that rhinacanthone-induced apoptosis in HeLa cells is mediated primarily through the mitochondria-dependent signaling pathway, suggesting that it may be a promising agent for the treatment of human cervical cancer.

Topics: Acanthaceae; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Benzopyrans; Blotting, Western; Cell Cycle; Cell Proliferation; DNA Fragmentation; Female; HeLa Cells; Humans; Naphthoquinones; Plant Roots; Reverse Transcriptase Polymerase Chain Reaction; Uterine Cervical Neoplasms

Rhinacanthone (1) and two 1,2-pyranonaphthoquinones (2,3) were synthesized and found to show very potent cytotoxicity against three cancer cell lines (KB, HeLa and HepG(2)) with IC(50) values of 0.92-9.63 microM, whereas the corresponding hydroxylated derivative 4 had reduced cytotoxicity (IC(50) values of 7.61-24.13 microM). Three 1,2-furanonaphthoquinone derivatives (5-7) were also synthesized with similar cytotoxicity as 1,2-pyranonaphthoquinones. In comparison to 1,2-naphthoquinones, six 1,4-naphthoquinones derivatives fused with pyran ring (8-10) and furan ring (11-13) were synthesized and they showed less cytotoxicity or inactive to the cancer cell lines. Moreover, compound 13 had significant cytotoxicity against HeLa cell line (IC(50) value of 9.25 microM) while it showed no toxic to vero cell.

Topics: Animals; Antineoplastic Agents; Benzopyrans; Cell Line, Tumor; Drug Screening Assays, Antitumor; Furans; Humans; Molecular Structure; Naphthoquinones; Pyrans

The antitumour activity of Rhinacanthone (3,4-dihydro-3,3-dimethyl-2H-naphtho-[1,2-B] pyran-5,6-dione) has been evaluated against Dalton's ascitic lymphoma (DAL) in Swiss albino mice. A significant enhancement of mean survival time of tumour bearing mice and peritoneal cell count in normal mice was observed with respect to the control group. When these Rhinacanthone treated animals underwent i.p. inoculation with DAL cells, tumour cell growth was found to be inhibited. After 14 d of inoculation, Rhinacanthone was able to reverse the changes in the haemotological parameters, protein and packed cellular volume consequent to tumour inoculation.

Topics: Animals; Antineoplastic Agents, Phytogenic; Ascitic Fluid; Benzopyrans; Lymphoma; Male; Mice; Naphthoquinones; Neoplasm Transplantation; Plant Extracts; Plants, Medicinal; Tumor Cells, Cultured