Antitrypanosomal potential of the red sea soft coral Nephthea mollis supported by metabolomics profiling and molecular docking studies

Khaled M. Allam; Yaser A. Mostafa; Usama R. Abdelmohsen; Amgad I.M. Khedr; Ahmed E. Allam; Ehab S. Elkhayat; Mostafa A. Fouad

doi:10.7324/JAPS.2023.117321

Abstract

The crude extract and its derived ethyl acetate fraction of the soft coral Nephthea mollis displayed remarkable in vitro antitrypanosomal activity against Trypanosoma brucei with IC50 values of 6.4 and 3.7 μg/ml, respectively. Consequently, the crude extract was subjected to LC–HR–ESI–MS metabolomics profiling to identify the constituents that may underlie their bioactivities. As a result, 33 secondary metabolites were characterized, among which sesquiterpenes and diterpenes prevailed. In silico molecular modeling revealed the high binding affinity for the ornithine decarboxylase active site, with five dereplicated compounds having docking scores higher than the cocrystallized ligand. These results highlight N. mollis as a rich source of compounds that might help develop therapies for Human African trypanosomiasis.

Keyword: Antitrypanosomal metabolomics profiling Nephthea mollis Trypanosoma brucei molecular docking ornithine decarboxylase

Citation:

Allam KM, Mostafa YA, Abdelmohsen UR, Khedr AIM, Allam AE, Fouad MA, Elkhayat ES. Antitrypanosomal potential of the red sea soft coral Nephthea mollis supported by metabolomics profiling and molecular docking studies. J Appl Pharm Sci, 2023. https://doi.org/10.7324/JAPS.2023.117321

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reference

Abdelhafez OH, Ali TFS, Fahim JR, Desoukey SY, Ahmed S, Behery FA, Kamel MS, Gulder TA, Abdelmohsen UR. Anti-inflammatory potential of green synthesized silver nanoparticles of the soft coral Nephthea sp. supported by metabolomics analysis and docking studies. Int J Nanomed, 2020; 15(1):5345-60. https://doi.org/10.2147/IJN.S239513

Abdelmohsen UR, Cheng C, Viegelmann C, Zhang T, Grkovic T, Ahmed S, Quinn RJ, Hentschel U, Edrada-Ebel RJMd. Dereplication strategies for targeted isolation of new antitrypanosomal actinosporins A and B from a marine sponge associated-Actinokineospora sp. EG49. Mar Drugs, 2014; 12(3):1220-44. https://doi.org/10.3390/md12031220

Abdelmohsen UR, Pimentel-Elardo SM, Hanora A, Radwan M, Abou-El-Ela SH, Ahmed S, Hentschel UJ. Isolation, phylogenetic analysis and anti-infective activity screening of marine sponge-associated Actinomycetes. Mar Drugs, 2010; 8(3):399-412. https://doi.org/10.3390/md8030399

Allam KM, Khedr AI, Allam AE, Abdelkader MSA, Elkhayat ES, Fouad MA. Chemical, and biological diversity in Nephthea soft corals in the current decade: a review. JABPS, 2021; 4(3):124-33. https://doi.org/10.21608/jabps.2021.62966.1121

Álvarez-Bardón M, Pérez-Pertejo Y, Ordóñez C, Sepúlveda-Crespo D, Carballeira NM, Tekwani BL, Murugesan S, Martinez-Valladares M, García- Estrada C, Reguera RMJMD. Screening marine natural products for new drug leads against trypanosomatids and malaria. Mar Drugs, 2020; 18(4):187. https://doi.org/10.3390/md18040187

Amir F, Koay YC, Yam WS. Chemical constituents and biological properties of the marine soft coral Nephthea: a review (Part 1). Trop J Pharm Res, 2012; 11(3):485-98. https://doi.org/10.4314/tjpr.v11i3.19

Ancheeva E, Daletos G, Proksch P. Lead compounds from mangrove-associated microorganisms. Mar Drugs, 2018; 16(9):319. https://doi.org/10.3390/md16090319

Bakr RO, Tawfike A, El-Gizawy HA, Tawfik N, Abdelmohsen UR, Abdelwahab MF, Alshareef WA, Fayez SM, El-Mancy SM, El-Fishawy AM, Abdelkawy MA, Fayed MA. The metabolomic analysis of five Mentha species: cytotoxicity, anti-helicobacter assessment, and the development of polymeric micelles for enhancing the anti-helicobacter activity. RSC Adv, 2021; 11(13):7318-30. https://doi.org/10.1039/D0RA09334C

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The protein data bank. Nucl Acids Res, 2000; 28(1):235-42. https://doi.org/10.1093/nar/28.1.235

Brun R, Blum J. Human African trypanosomiasis. Infect Dis Clin, 2012; 26(2):261-73. https://doi.org/10.1016/j.idc.2012.03.003

Cos P, Vlietinck AJ, Berghe DV, Maes L. Anti-infective potential of natural products: how to develop a stronger in vitro proof-of-concept'. J Ethnopharmacol, 2006; 106(3):290-302. https://doi.org/10.1016/j.jep.2006.04.003

De Koning PH. The drugs of sleeping sickness: their mechanisms of action and resistance, and a brief history. Trop Med Infect Dis, 2020; 5(1):14. https://doi.org/10.3390/tropicalmed5010014

Duh CY, Wang SK, Weng YL, Chiang MY, Dai FJ. Cytotoxic terpenoids from the Formosan soft coral Nephthea brassica. J Nat Prod, 1999; 62(11):1518-21. https://doi.org/10.1021/np990212d

El-Gamal AA, Wang SK, Dai CF, Duh CY. New nardosinanes and 19-oxygenated ergosterols from the soft coral Nephthea armata collected in Taiwan. J Nat Prod, 2004; 67(9):1455-8. https://doi.org/10.1021/np0400858

Elmaidomy AH, Mohammed R, Hassan HM, Owis AI, Rateb ME, Khanfar MA, Krischke M, Mueller MJ, Abdelmohsen UR. Metabolomic profiling and cytotoxic tetrahydrofurofuran lignans investigations from Premna odorata Blanco. Metabolites, 2019; 9(10):223. https://doi.org/10.3390/metabo9100223

Gayer M, Legros D, Formenty P, Connolly MA. Conflict and emerging infectious diseases. Emerg Infect Dis, 2007; 13(11): 1625-31. https://doi.org/10.3201/eid1311.061093

Handayani D, Edrada RA, Proksch P, Wray V, Witte L, van Ofwegen L, Kunzmann A. New oxygenated sesquiterpenes from the Indonesian soft coral Nephthea chabrolii. J Nat Prod, 1997; 60(7):716-8. https://doi.org/10.1021/np960699f

Hu J, Yang B, Lin X, Zhou X, Yang X, Long L, Liu Y. Chemical and biological studies of soft corals of the Nephtheidae family. Chem Biodivers, 2011; 8(6):1011-32. https://doi.org/10.1002/cbdv.201000105

Huber W, Koella JC. A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites. Acta Trop, 1993; 55(4):257-61. https://doi.org/10.1016/0001-706X(93)90083-N

Ibezim A, Debnath B, Ntie-Kang F, Mbah CJ, Nwodo NJ. Binding of antitrypanosomal natural products from African flora against selected drug targets: a docking study. Med Chem Res, 2017a; 26(3):562-79. https://doi.org/10.1007/s00044-016-1764-y

Ibezim A, Nwodo NJ, Nnaji NJ, Ujam OT, Olubiyi OO, Mba CJ. In silico investigation of morpholines as a novel class of trypanosomal triosephosphate isomerase inhibitors. Med Chem Res, 2017b; 26(1):180-9. https://doi.org/10.1007/s00044-016-1739-z

Jackson LK, Goldsmith EJ, Phillips MA. X-ray structure determination of Trypanosoma brucei ornithine decarboxylase bound to D-ornithine and to G418: insights into substrate binding and ODC conformational flexibility. J Biol Chem, 2003; 278(24):22037-43. https://doi.org/10.1074/jbc.M300188200

Jacob M, Lopata AL, Dasouki M, Abdel Rahman AM. Metabolomics toward personalized medicine. Mass Spectrom Rev, 2019; 38(3):221-38. https://doi.org/10.1002/mas.21548

Kapojos MM, Mangindaan REP, Nakazawa T, Oda T, Ukai K, Namikoshi MJC. Three new nardosinane type sesquiterpenes from an Indonesian soft coral Nephthea sp. Chem Pharm Bull, 2008; 56(3):332-4. https://doi.org/10.1248/cpb.56.332

Kitagawa I, Cui Z, Son BW, Kobayashi M, Kyogoku YJC. Marine natural products. XVII. Nephtheoxydiol, a new cytotoxic hydroperoxy-germacrane sesquiterpene, and related sesquiterpenoids from an Okinawan soft coral of Nephthea sp. (Nephtheidae). Chem Pharm Bull, 1987; 35(1):124-35. https://doi.org/10.1248/cpb.35.124

Kjer J, Debbab A, Aly AH, Proksch P. Methods for isolation of marine-derived endophytic fungi and their bioactive secondary products. Nat Protoc, 2010; 5(3):479-90. https://doi.org/10.1038/nprot.2009.233

Lotfy MM, Sayed AM, AboulMagd AM, Hassan HM, El Amir D, Abouzid SF, El-Gendy AO, Rateb ME, Abdelmohsen UR, Alhadrami H, Mohammed R. Metabolomic profiling, biological evaluation of Aspergillus awamori, the river Nile-derived fungus using epigenetic and OSMAC approaches. RSC Adv, 2021; 11(12):6709-19. https://doi.org/10.1039/D0RA07578G

Macintyre L, Zhang T, Viegelmann C, Martinez IJ, Cheng C, Dowdells C, Abdelmohsen UR, Gernert C, Hentschel U, Edrada-Ebel R. Metabolomic tools for secondary metabolite discovery from marine microbial symbionts. Mar Drugs, 2014; 12(6):3416-48. https://doi.org/10.3390/md12063416

Mahmoud BK, Hamed ANE, Samy MN, Abdelmohsen UR, Attia EZ, Fawzy MA, Refaey RH, Salem MA, Pimentel-Elardo SM, Nodwell JR, Desoukey SY, Kamel MS. Metabolomic profiling and biological investigation of Tabebuia Aurea (Silva Manso) leaves, family Bignoniaceae. Nat Prod Res, 2021; 35(22):4632-7. https://doi.org/10.1080/14786419.2019.1698571

Molyneux DH, Savioli L, Engels D. Neglected tropical diseases: progress towards addressing the chronic pandemic. Lancet, 2017; 21(1):312-25. https://doi.org/10.1016/S0140-6736(16)30171-4

Pays E. Expression and function of surface proteins in Trypanosoma brucei. Mol Biochem Parasitol, 1999; 91(1):3-36. https://doi.org/10.1016/S0166-6851(97)00183-7

Said AAE, Afifi AH, Ali TF, Samy MN, Abdelmohsen UR, Fouad MA, Attia EZ. NS3/4A helicase inhibitory alkaloids from Aptenia cordifolia as HCV target. RSC Adv, 2021; 11(52):32740-9. https://doi.org/10.1039/D1RA06139A

Scholz C, Knorr S, Hamacher K, Schmidt B. DOCKTITE-a highly versatile step-by-step workflow for covalent docking and virtual screening in the molecular operating environment. J Chem Inf Model, 2015; 55(2):398-406. https://doi.org/10.1021/ci500681r

Shady NH, Elfakharany Z, Salem MA, Ahmed S, Fouad MA, Kamel MS, Krischke M, Mueller MJ, Abdelmohsen UR. Dereplication analysis and antitrypanosomal potential of the red sea sponge Amphimedon sp. supported by molecular modeling. Rev Bras Farmacogn, 2020; 30: 290-4. https://doi.org/10.1007/s43450-020-00053-1

Steverding D. The development of drugs for treatment of sleeping sickness: a historical review. Parasit Vectors, 2010; 3(1):1-9. https://doi.org/10.1186/1756-3305-3-15

Su JH, Dai CF, Huang HH, Wu YC, Sung PJ, Hsu CH, Sheu JH. Terpenoid-related metabolites from a formosan soft coral Nephthea chabrolii. Chem Pharm Bull, 2007; 55(4):594-7. https://doi.org/10.1248/cpb.55.594

Tawfike AF, Viegelmann C, Edrada-Ebel R. Metabolomics and dereplication strategies in natural products. Methods Mol Biol, 2013; 1055:227-44. https://doi.org/10.1007/978-1-62703-577-4_17

Ueno AK, Barcellos AF, Costa-Silva TA, Mesquita JT, Ferreira DD, Tempone AG, Romoff P, Antar GM, Lago JHG. Antitrypanosomal activity and evaluation of the mechanism of action of diterpenes from aerial parts of Baccharis retusa (Asteraceae). Fitoterapia, 2018; 125:55-8. https://doi.org/10.1016/j.fitote.2017.12.016

Yuliana ND, Khatib A, Choi YH, Verpoorte R. Metabolomics for bioactivity assessment of natural products. Phytother Res, 2011; 25(2): 157-69. https://doi.org/10.1002/ptr.3258

Zeouk I, Sifaoui I, López-Arencibia A, Reyes-Batlle M, Bethencourt-Estrella CJ, Bazzocchi IL, Bekhti K, Lorenzo-Morales J, Jiménez IA, Piñero JE. Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids. Biomed Pharmacother, 2020; 130: 110518. https://doi.org/10.1016/j.biopha.2020.110518

Zhang WH, Williams ID, Che CT. Chabrolols A, B and C, three new norditerpenes from the soft coral Nephthea chabroli. Tetrahedron Lett, 2001; 42(28):4681-5. https://doi.org/10.1016/S0040-4039(01)00837-1

Abstract

HTML Full Text

Reference

Article Metrics

Related Search

Citiaion Alert By Google Scholar

Similar Articles