Isochondodendrine and 2′-norcocsuline: additional alkaloids from Triclisia subcordata induce cytotoxicity and apoptosis in ovarian cancer cell lines

Abstract

Triclisia subcordata Oliv (Menispermeaceae) is used in herbal medicine for the treatment of cancer and other diseases in Africa. This study aims to isolate minor alkaloids present in this plant and assay their cytotoxic activities. Isochondodendrine and 2 0 -norcocsuline as two minor alkaloids together with the abundant cycleanine were isolated and identified by mass spectrometry and NMR spectroscopy. Both isochondodendrine and 2 0 -norcocsuline exhibited in vitro cytotoxicity in four ovarian cancer cell lines (A2780, IGROV-1, OVCAR-8, and OVCAR-4) with IC 50 ranges of 3.5-17 mM and 0.8-6.2 mM respectively.These alkaloids showed mostly slightly weaker potencies when tested using normal human ovarian epithelial cells, IC 50 ¼ 10.5 AE 1.2 mM and 8.0 AE 0.2 mM for isochondodendrine and 2 0 -norcocsuline, respectively. The alkaloids induced apoptosis in ovarian cancer cells because they activated caspases 3/7, induced cleavage of PARP, increased the subG 1 population in cell cycle analysis and increased Annexin V/propidium iodide staining. These observations suggest that isochondodendrine and 2 0 -norcocsuline contributing to the cytotoxic activity of T. subcordata may be suitable starting points for the future development of novel therapeutics to treat ovarian cancer.

Palmatine from Unexplored Rutidea parviflora Showed Cytotoxicity and Induction of Apoptosis in Human Ovarian Cancer Cells

“…A number of plant-derived or semi-synthetic anti-ovarian cancer drugs including paclitaxel, etoposide and topotecan have been approved and widely used in clinic [13,14]. Previously, we identified cytotoxic cyclotides from a Chinese medicinal plant [15], a cytotoxic indolizine alkaloid, securinine [16,17], and three cytotoxic bisbenzylisoquinoline alkaloids, cycleanine [18,19,20], isochondodendrine and 2’-norcocsuline [21,22] in Nigerian medicinal plants. Semi-synthetic cycleanine [23] and thymoquinone [24] analogues were further prepared and evaluated for their in vitro anti-ovarian cancer activities.…”

Secondary metabolites from Triclisia gilletii (De Wild) Staner (Menispermaceae) with antimycobacterial activity against Mycobacterium tuberculosis

“…In some areas, the plant is used in the treatment of several ailments such as: malaria, venereal diseases, epileptic attacks, edema, anemia, diarrhea, stomach problems, leprosy, mental health problems, dysentery, respiratory diseases and convulsive coughing (Bouquet 1969;Kokwaro 1993;Burkill 1997;Neuwinger 1998;Mesia et al 2008). According to the literature data, Triclisia species contains mainly bisbenzylisoquinoline (BBIQ) alkaloids (Schiff 1983;Murebwayire et al 2006Murebwayire et al , 2009Uche et al 2017), morphinan alkaloids (Spiff et al 1981) and other amide alkaloids (Murebwayire et al 2006;Samita et al 2017). Previous reports from T. gilletii revealed the presence of BBIQ (Tackie et al 1973;Dwuma-Badu et al 1975;Owusu et al 1981).…”

Synthesis of (aminoalkyl)cycleanine analogues: cytotoxicity, cellular uptake, and apoptosis induction in ovarian cancer cells

“…These were consistent with unmodified cycleanine and other BBIQ alkaloids. 4,5 Importantly, using analogue 3 appended with a propargyl group its cellular uptake in cancer cells was clearly demonstrated via click chemistry and fluorescence microscopy. The semi-synthesis of additional BBIQ alkaloid analogues using the established approach to gain structureactivity relationship, and identification of protein targets in the cancer cells using a chemical proteomics approach 33,34 are ongoing in our laboratory.…”

“…BBIQ alkaloids are prevalent in the families like Menispermeaceae, Annonaceae, Berberidaceae, Monimaiaceae and Ranunuclaceae. [1][2][3] The BBIQ alkaloids were reported to exhibit anti-ovarian, [4][5][6][7] -lung, 8 bladder, 9 -colorectal, 10 -gallbladder carcinoma and -prostate 11 cancer activities. 12,13 The use of isolated natural products as scaffolds to generate their analogues via chemical transformation is a promising and successful approach in drug discovery.…”

“…by us and they showed potent in vitro anti-ovarian cancer activity. [4][5][6] Among them, cycleanine (1) is bioactive, with the highest therapeutic index and the most abundant component (1.1%). 4 Therefore cycleanine was preferred as a hit compound for chemical modification.…”