In Vitro Schistosomicidal Activity of Balsaminol F and Karavilagenin C

 

 Buy Article Permissions and Reprints

Abstract

Five cucurbitane-type triterpenes (1–5), previously isolated from the African medicinal plant Momordica balsamina, along with five ester derivatives (6–10) of karavilagenin C (2), were evaluated for their potential schistosomicidal activity against Schistosoma mansoni adult worms. The natural compounds were isolated from the ethyl acetate-soluble fraction of the methanol extract of the aerial parts of M. balsamina. In a preliminary study, a significant schistosomicidal activity was observed for both the crude methanol extract and the ethyl acetate fraction. The compounds responsible for the activity were found to be balsaminol F (1) and karavilagenin C (2) with LC₅₀ values of 14.7 ± 1.5 and 28.9 ± 1.8 µM, respectively, after 24 h of incubation (positive control praziquantel, LC₅₀ = 1.2 ± 0.1 µM). Both compounds (1, 2), at 10–50 µM, induced significant reductions in the motor activity of the worms and significantly decreased the egg production. Furthermore, they were able (at 10–100 µM) to separate the adult worm pairs into male and female after 24 h. Compounds 3–5, bearing a sugar moiety as a substituent, and the acylated derivatives of karavilagenin C (6–10) were inactive, suggesting that the presence of free hydroxyl groups in the tetracyclic skeleton might be important for the activity. A correlation between activity and the molecular volume/weight of compounds was also found.

• References

• 1 Chitsulo L, Engles D, Montresor A, Savioli L. The global status of schistosomiasis and its control. Acta Trop 2000; 77: 41-51
  CrossrefPubMedGoogle Scholar
• 2 WHO. Schistosomiasis: number of people treated worldwide in 2009. Weekly Epidemiological record, Vol. 86. Geneva: World Health Organization; 2011: 73-80
  Google Scholar
• 3 Doenhoff MJ, Hagan P, Cioli D, Southgate V, Pica-Mattoccia L, Botros S, Coles G, Tchuem Tchuenté LA, Mbaye A, Engels D. Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs. Parasitology 2009; 136: 1825-1835
  CrossrefPubMedGoogle Scholar
• 4 Fallon PG, Tao LF, Ismail MM, Bennett JL. Schistosome resistance to praziquantel: fact or artifact. Trends Parasitol 1996; 12: 316-320
  PubMedGoogle Scholar
• 5 Magalhães LG, Kapadia GJ, Tonuci LRS, Caixeta SCC, Parreira NA, Rodrigues V, Da Silva Filho AA. In vitro schistosomicidal effects of phloroglucinol derivatives from Dryopteris species against Schistosoma mansoni adult worms. Parasitol Res 2010; 106: 395-401
  CrossrefPubMedGoogle Scholar
• 6 Melek FR, Tadros MM, Yousif F, Selim MA, Hassan MH. Screening of marine extracts for schistosomicidal activity in vitro. Isolation of the triterpene glycosides echinosides A and B with potential activity from the Sea Cucumbers Actinopyga echinites and Holothuria polii . Pharm Biol 2012; 50: 490-496
  CrossrefPubMedGoogle Scholar
• 7 Moraes J, Nascimento C, Lopes PO, Nakano E, Yamaguchi LF, Kato MJ, Kawano T. Schistosoma mansoni: In vitro schistosomicidal activity of piplartine. Exp Parasitol 2011; 127: 357-364
  CrossrefPubMedGoogle Scholar
• 8 Pereira AC, Magalhães LG, Gonçalves UO, Luz PP, Moraes AC, Rodrigues V, da Matta Guedes PM, da Silva Filho AA, Cunha WR, Bastos JK, Nanayakkara NP, de Silva ML. Schistosomicidal and trypanocidal structure-activity relationships for (±)-licarin A and its (−)- and (+)-enantiomers. Phytochemistry 2011; 72: 1424-1430
  CrossrefPubMedGoogle Scholar
• 9 Miranda MA, Magalhães LG, Tiossi RF, Kuehn CC, Oliveira LG, Rodrigues V, McChesney JD, Bastos JK. Evaluation of the schistosomicidal activity of the steroidal alkaloids from Solanum lycocarpum fruits. Parasitol Res 2012; 111: 257-262
  CrossrefPubMedGoogle Scholar
• 10 Murthy PK, Joseph SK. Plant products in the treatment and control of filariasis and other helminth infections and assay systems for antifilarial/anthelmintic activity. Planta Med 2011; 77: 647-661
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Thakur GS, Bag M, Sanodiya BS, Bhadauriya P, Debnath M, Prasad G, Bisen PS. Momordica balsamina: a medicinal and neutraceutical plant for health care management. Curr Pharm Biotechnol 2009; 10: 667-682
  CrossrefPubMedGoogle Scholar
• 12 Bandeira SO, Gaspar F, Pagula FP. African ethnobotany and healthcare: emphasis on Mozambique. Pharm Biol 2001; 39: 70-73
  PubMedGoogle Scholar
• 13 Van de Venter M, Roux S, Bungu LC, Louw J, Crouch NR, Grace OM, Maharaj V, Pillay P, Sewnarian P, Bhagwandin N, Folb P. Antidiabetic screening and scoring of 11 plants traditionally used in South Africa. J Ethnopharmacol 2008; 119: 81-86
  CrossrefPubMedGoogle Scholar
• 14 Ramalhete C, Lopes D, Mulhovo S, Molnár J, Rosário VE, Ferreira MJ. New antimalarials with a triterpenic scaffold from Momordica balsamina . Bioorg Med Chem 2010; 18: 5254-5260
  CrossrefPubMedGoogle Scholar
• 15 Ramalhete C, Lopes D, Molnár J, Mulhovo S, Rosário VE, Ferreira MJ. Karavilagenin C derivatives as antimalarials. Bioorg Med Chem 2011; 19: 330-338
  CrossrefPubMedGoogle Scholar
• 16 Ramalhete C, da Cruz FP, Lopes D, Mulhovo S, Rosário VE, Prudêncio M, Ferreira MJ. Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections. Bioorg Med Chem 2011; 19: 7474-7481
  CrossrefPubMedGoogle Scholar
• 17 De Tommasi N, De Simone F, De Feo V, Pizza C. Phenylpropanoid glycosides and rosmarinic acid from Momordica balsamina . Planta Med 1991; 57: 201
  Article in Thieme ConnectPubMedGoogle Scholar
• 18 De Tommasi N, De Simone F, Piacente S, Pizza C, Mahmood N. Diterpenes from Momordica balsamina . Nat Prod Lett 1995; 6: 261-268
  CrossrefPubMedGoogle Scholar
• 19 Ramalhete C, Lopes D, Mulhovo S, Molnár J, Rosário VE, Ferreira MJ. New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells. Bioorg Med Chem 2009; 17: 6942-6951
  CrossrefPubMedGoogle Scholar
• 20 Smithers SR, Terry RJ. Infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology 1965; 55: 695-700
  CrossrefPubMedGoogle Scholar
• 21 Manneck T, Haggenmüller Y, Keiser J. Morphological effects and tegumental alterations induced by mefloquine on schistosomula adult flukes on Schistosoma mansoni . Parasitology 2010; 137: 85-98
  CrossrefPubMedGoogle Scholar
• 22 Michaels RM, Prata A. Evolution and characteristics of Schistosoma mansoni eggs laid in vitro . J Parasitol 1968; 54: 921-930
  CrossrefPubMedGoogle Scholar
• 23 de Araújo SC, de Mattos AC, Teixeira HF, Coelho PM, Nelson DL, de Oliveira MC. Improvement of in vitro efficacy of a novel schistosomicidal drug by incorporation into nanoemulsions. Int J Pharm 2007; 337: 307-315
  CrossrefPubMedGoogle Scholar
• 24 Comley JCW, Rees MJ, Turner CH, Jenkins DC. Calorimetric quantitation of filarial viability. Int J Parasitol 1989; 19: 77-83
  CrossrefPubMedGoogle Scholar
• 25 Wink M. Evolutionary advantage and molecular modes of action of multi-component mixtures used in phytomedicine. Curr Drug Metab 2008; 9: 996-1009
  CrossrefPubMedGoogle Scholar
• 26 Han HK, Amidon GL. Targeted prodrug design to optimize drug delivery. AAPS PharmSci 2000; 2: E6
  PubMedGoogle Scholar