A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii

Abstract

Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2–13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 μg/mL. The isolated metabolites dichamanetin, (E)-acetylmelodorinol, and cleistenolide showed IC50 = 9.3, 7.6 and 15.2 μM, respectively, against P. falciparum 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC50 = 42.0 μg/mL (crude extract) and 9.6–30.7 μM (isolated compounds). Our findings demonstrate the potential applicability of C. kirkii as a source of antimalarial and anticancer agents.

Review of phytochemistry, biological activities and therapeutic potential of Cleistochlamys kirkii

“…Leaf and root decoction taken orally (Bruschi et al, 2011) Rheumatism Leaf decoction applied topically (Verzar and Petri, 1987;Nyandoro et al, 2019)…”

“…The compounds cleistodienediol, cleistodienol A, cleistodienol B and acetylmelodorinol exhibited activities against both 3D7 and Dd2 with half-maximal inhibitory concentration (IC 50 ) values ranging from 0.2 µM to 40.0 µM (Nyandoro et al, 2017). Similarly, (Nyandoro et al, 2019) evaluated the antiplasmodial activities of ethanolic crude extract of C. kirkii root bark and the compounds cleistonol, chamanetin, isochamanetin, dichamanetin, 7methoxyisochamanetin, pinostrobin, pinocembrin, benzyl benzoate, 2-methoxybenzyl benzoate, guaiol, polycarpol, (E)-acetylmelodorinol and cleistenolide isolated from the species against the chloroquinesensitive strain of Plasmodium falciparum 3D7 using an imaging-based assay method with artesunate as the reference drug. The crude extract gave 72.0% inhibition against the 3D7 strain at 0.01 µg/mL, while the compounds dichamanetin, (E)acetylmelodorinol and cleistenolide exhibited IC 50 values of 9.3 µM, 7.6 µM and 15.2 µM, respectively, against 3D7 (Nyandoro et al, 2019).…”

“…Similarly, (Nyandoro et al, 2019) evaluated the antiplasmodial activities of ethanolic crude extract of C. kirkii root bark and the compounds cleistonol, chamanetin, isochamanetin, dichamanetin, 7methoxyisochamanetin, pinostrobin, pinocembrin, benzyl benzoate, 2-methoxybenzyl benzoate, guaiol, polycarpol, (E)-acetylmelodorinol and cleistenolide isolated from the species against the chloroquinesensitive strain of Plasmodium falciparum 3D7 using an imaging-based assay method with artesunate as the reference drug. The crude extract gave 72.0% inhibition against the 3D7 strain at 0.01 µg/mL, while the compounds dichamanetin, (E)acetylmelodorinol and cleistenolide exhibited IC 50 values of 9.3 µM, 7.6 µM and 15.2 µM, respectively, against 3D7 (Nyandoro et al, 2019). (Samwel et al, 2007) evaluated the cytotoxicity activities of the compounds cleistodienol, (Z)-(+)-5-(2,3-dihydroxy-propylidene)-5H-furan-2-one, melodorinol, acetyl melodorinol, iso-acetyl melodorinol and benzoyl melodorinol isolated from the fruits, leaves, roots and stems of C. kirkii using the brine shrimp assay.…”

“…The compounds cleistodienediol, cleistodienol A, cleistodienol B, cleistenechlorohydrin A, cleistenechlorohydrin B, cleistenediol F, cleistenonal, cleistophenolide, ent-subglain C, melodorinol, acetylmelodorinol, tetramethylscutellarein and 2-hydroxybenzaldehyde isolated from the species against HEK-293 cells and MDA-MB-231, triple-negative, aggressive breast cancer cell line. All the compounds exhibited activities with IC 50 values ranging from 0.03 µM to 8.2 µM (Nyandoro et al, 2019). (Nyandoro et al, 2019) also evaluated the cytotoxicity activities of ethanolic crude extract of C. kirkii root bark and the compounds cleistonol, chamanetin, isochamanetin, dichamanetin, 7methoxyisochamanetin, pinostrobin, pinocembrin, benzyl benzoate, 2-methoxybenzyl benzoate, guaiol, polycarpol, (E)-acetylmelodorinol and cleistenolide isolated from the species against the triple-negative aggressive breast cancer cell line MDA-MB-231 using Alamar Blue assay with lupeol as the reference drug.…”

“…All the compounds exhibited activities with IC 50 values ranging from 0.03 µM to 8.2 µM (Nyandoro et al, 2019). (Nyandoro et al, 2019) also evaluated the cytotoxicity activities of ethanolic crude extract of C. kirkii root bark and the compounds cleistonol, chamanetin, isochamanetin, dichamanetin, 7methoxyisochamanetin, pinostrobin, pinocembrin, benzyl benzoate, 2-methoxybenzyl benzoate, guaiol, polycarpol, (E)-acetylmelodorinol and cleistenolide isolated from the species against the triple-negative aggressive breast cancer cell line MDA-MB-231 using Alamar Blue assay with lupeol as the reference drug. The crude extract exhibited activities with an IC 50 value of 42.0 µg/mL.…”