Antiplasmodial and Cytotoxic Activities of Extracts from Jacaranda mimosifolia and Pseudospondias microcarpa

International audienc

Antiplasmodial and cytotoxic activity of lanostane type triterpenoids isolated from Leplaea mayombensis

International audienceLeplaeric acid E 5, leplazarin 6a and 21-epileplazarin 6b, three new 3,4-seco-lanostane type triterpenes have been isolated from the stem bark of Leplaea mayombensis (Pellegr.) Staner along with fourteen known compounds from the fruits and roots. Leplaeric acid E, leplazarin and 21-epileplazarin, 15-α-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid, mayomlactones A and B, lanosta-7,24-dien-3-one, leplaeric acid A, B and C were screened in vitro for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum and for cytotoxicity against CAL-27, CaCo2, Skov-3, and HepG2 cells line. Three compounds including 15-α-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (IC50 5.65–7.09 μM), lanosta-7,24-dien-3-one (IC50 7.18–9.07 μM), and leplaeric acid C (IC50 7.59–8.47 μM) were the most active against both strains of P. falciparum. All the compounds exhibited cytotoxicity against the three-cell lines with IC50 ranging from 12.30 to 181.88 μM. These results confirm the usage of the medicinal plant L. mayombensis for the management of malaria and suggest that further lead optimization studies on potent compounds identified from this study could lead to the identification of potential of lead molecules as scaffold for new antimalarial drug discovery

Antiproliferative activity of naphthoquinones and indane carboxylic acids from lapachol against a panel of human cancer cell lines

Lapachol (1) is a well-studied natural product isolated from plants of the Bignoniaceae family and demonstrates diverse biological effects. Historically, chemical transformation of the lapachol scaffold has yielded new derivatives with impressive biological activity and rich chemical diversity. β-lapachone (2), α-lapachone (3), and 2-acetylfuronaphthoquinone (4) are examples of analogs derived from lapachol that show superior antitumor activity compared with the natural product. In the present study, novel indane carboxylic acid: 2,2-dimethyl-2,3-dihydroindeno[1,2-b]pyran-4,5-dione (9) and methyl 5-hydroxy-2,2-dimethyl-2,3,4,5-tetrahydroindeno[1,2-b]pyran-5-carboxylate (10) and naphthoquinone derivatives were synthesized from lapachol with structural similarities to the antitumor lapachol derivatives. The synthesized compounds were evaluated for antiproliferative activities against a panel of human cancer cell lines including in vitro models for neuroblastoma, melanoma, glioblastoma, and non-small cell lung cancer. As expected, the most potent derivatives were those incorporating β-naphthoquinone and α-naphthoquinono[2,3-b]furan skeletons. Many of these compounds possessed nanomolar to single digit micromolar antiproliferative potency. However, the most interesting analog evaluated was the dione 9 with an indeno[1,2-b]pyran skeleton, which demonstrated potent cytotoxic activity. The current investigation identified several new lead compounds that could be used as starting points for anticancer drug discovery.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Antiproliferative and cytotoxic secondary metabolites from fruits of <i>Leplaea mayombensis</i>

<p>Two new <i>seco</i>-lanostane-type triterpenes, named mayomlactones A (<b>1</b>) and B (<b>2</b>) were isolated from the fruits of <i>Leplaea mayombensis</i> together with 10 known compounds (<b>3</b>–<b>12</b>). Structures of the new compounds were elucidated by extensive spectroscopic studies. Except compounds <b>11</b> and <b>12</b>, all the other chemical compounds are newly reported from <i>Leplaea</i> genus. From the results of this investigation, compounds <b>1</b>–<b>10</b> were examined for antiproliferative activity against HeLa cells as well as cytotoxicity against 3T3 cell line. Compounds <b>3</b> and <b>4</b> showed moderate antiproliferative activity with IC₅₀ values of 10.4 ± 0.1 and 18.6 ± 0.2 μM, respectively. On the other hand, compounds <b>1</b>, <b>4</b> and <b>9</b> showed weak cytotoxicity with IC₅₀ values 44.1 ± 0.5, 55.8 ± 0.7 and 55.1 ± 0.5 μM. Overall, none of the tested compounds showed good selectivity (SI ranging from 0.51 to 3.06) but high toxicity against the 3T3 cell line.</p