Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

doi:10.1007/s13659-017-0125-y

应用天然产物 ›› 2017, Vol. 7 ›› Issue (3): 235-247.DOI: 10.1007/s13659-017-0125-y

• Original article • 上一篇下一篇

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Kennedy D. Nyongbela^1,2, Fidele Ntie-Kang³, Thomas R. Hoye², Simon M. N. Efange¹

1. Pharmacochemistry Research Group, Department of Chemistry, University of Buea, P. O. Box 63, Buea, Cameroon;
2. Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, MN, USA;
3. Chemical and Bioactivity Information Centre, Department of Chemistry, University of Buea, P. O. Box 63, Buea, Cameroon

收稿日期:2016-12-25 修回日期:2017-03-23 出版日期:2017-06-24 发布日期:2018-02-06
通讯作者: Kennedy D.Nyongbela,e-mail:knyongbela@gmail.com
基金资助:
We are grateful for financial support from the International Cooperative Biodiversity Groups (ICBG),a program of the Fogarty International Centre of the National Institutes of Health (NIH),USA through grant (no TW00327) awarded to Professor S. M.N.Efange and Medicines for Malaria Venture (MMV),Geneva, Switzerland.The US Fulbright Council for International Exchange of Scholars (CIES) is acknowledged for grant to Kennedy D.Nyongbela to carry-out research at the University of Minnesota.We wish to thank M.Campbell and A.Powell from the Centre for Drug Candidate Optimisation (CDCO),Monash University for the DMPK data.Fidele Ntie-Kang is currently a Georg Forster fellow of the Alexander von Humboldt Foundation,Germany.We are equally grateful to Schrödinger Inc.for the academic license to use the QikProp software.

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Kennedy D. Nyongbela^1,2, Fidele Ntie-Kang³, Thomas R. Hoye², Simon M. N. Efange¹

1. Pharmacochemistry Research Group, Department of Chemistry, University of Buea, P. O. Box 63, Buea, Cameroon;
2. Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, MN, USA;
3. Chemical and Bioactivity Information Centre, Department of Chemistry, University of Buea, P. O. Box 63, Buea, Cameroon

Received:2016-12-25 Revised:2017-03-23 Online:2017-06-24 Published:2018-02-06
Supported by:
We are grateful for financial support from the International Cooperative Biodiversity Groups (ICBG),a program of the Fogarty International Centre of the National Institutes of Health (NIH),USA through grant (no TW00327) awarded to Professor S. M.N.Efange and Medicines for Malaria Venture (MMV),Geneva, Switzerland.The US Fulbright Council for International Exchange of Scholars (CIES) is acknowledged for grant to Kennedy D.Nyongbela to carry-out research at the University of Minnesota.We wish to thank M.Campbell and A.Powell from the Centre for Drug Candidate Optimisation (CDCO),Monash University for the DMPK data.Fidele Ntie-Kang is currently a Georg Forster fellow of the Alexander von Humboldt Foundation,Germany.We are equally grateful to Schrödinger Inc.for the academic license to use the QikProp software.

摘要/Abstract

摘要： The antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1-6), isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is reported. The study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The in silico method employed a total of 46 descriptors, calculated using Schrödinger QikProp software. 18 of these molecular descriptors that are often used to predict DMPK profiles of drug-like molecules have been selected for discussion. In vitro experimental assessment of metabolic stability made use of human liver microsomes, which was used to correlate theoretical predictions with experimental findings. Overall, the test compounds have been found to have acceptable physicochemical properties and fall within the ranges associated with “drug-like” molecules. Moreover, the compounds exhibited minimal degradation in incubations with human liver microsomes. Although some of these compounds have been reported previously (1, 2, 4 and 5), this is the first report on their antiparasitic activities, as well as assessment of their DMPK profiles. These results have therefore provided a window for further development of this novel class of sesquiterpene molecules as potential antiparasitic drugs.

关键词: Sesquiterpenes, Pharmacokinetics, Drug metabolism, Scleria striatinux

Abstract: The antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1-6), isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is reported. The study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The in silico method employed a total of 46 descriptors, calculated using Schrödinger QikProp software. 18 of these molecular descriptors that are often used to predict DMPK profiles of drug-like molecules have been selected for discussion. In vitro experimental assessment of metabolic stability made use of human liver microsomes, which was used to correlate theoretical predictions with experimental findings. Overall, the test compounds have been found to have acceptable physicochemical properties and fall within the ranges associated with “drug-like” molecules. Moreover, the compounds exhibited minimal degradation in incubations with human liver microsomes. Although some of these compounds have been reported previously (1, 2, 4 and 5), this is the first report on their antiparasitic activities, as well as assessment of their DMPK profiles. These results have therefore provided a window for further development of this novel class of sesquiterpene molecules as potential antiparasitic drugs.

Key words: Sesquiterpenes, Pharmacokinetics, Drug metabolism, Scleria striatinux

Kennedy D. Nyongbela, Fidele Ntie-Kang, Thomas R. Hoye, Simon M. N. Efange. Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment[J]. 应用天然产物, 2017, 7(3): 235-247.

参考文献

1. WHO, Global report for research on infectious diseases of poverty (2012). http://whqlibdoc.who.int/publications/2012/9789241564489_eng.pdf Accessed on 18 Dec 2016
2. M. Jung, H. Kim, K. Lee, M. Park, Mini-Rev. Med. Chem. 3, 159-165 (2003)
3. H. Noedl, Y. Se, K. Schaecher, B.L. Smith, D. Socheat, M.M. Fukuda, N. Engl. J. Med. 359, 2619-2620 (2008)
4. M. Balasegaram, S. Harris, F. Checchi, S. Ghorashian, C. Hamel, U. Karunakarab, Bull. World Health Organ. 84, 10 (2006)
5. K. Hostettmann, A. Marston, K. Ndjoko, J.L. Wolfender, Curr. Org. Chem. 4, 973-1010 (2000)
6. D.J. Newman, J. Med. Chem. 51, 2589-2599 (2008)
7. A.L. Harvey, Drug Discov. Today 13, 894-901 (2008)
8. S.M.N. Efange, Advances in phytomedicine, in Natural Products:A Continuing Source of Inspiration for the Medicinal Chemist, ed. by M.M. Iwu, J.C. Wootton (Elsevier Science, Amsterdam, 2002), pp. 61-69
9. F. Darvas, G. Keseru, A. Papp, G. Dorman, L. Urge, P. Krajcsi, Top. Med. Chem. 2, 1287-1304 (2002)
10. J. Hodgson, Nat. Biotechnol. 19, 722-726 (2001)
11. M.A. Navia, P.R. Chaturvedi, Drug Dev. Today 1, 179-189 (1996)
12. C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Adv. Drug Deliv. Rev. 23, 3-25 (2001)
13. M.P. Gleeson, A. Hersey, S. Hannongbua, Curr. Top. Med. Chem. 11(4), 358-381 (2011)
14. C.A. Lipinski, J. Pharmacol. Toxicol. Methods 44, 235-249 (2000)
15. J.A. DiMasi, R.W. Hansen, H.G. Grabowsk, J. Health Econ. 22, 151-185 (2003)
16. R.N. Ndip, A.E.M. Tarkang, S.M. Mbullah, H.N. Luma, A. Malongue, L.M. Ndip, K. Nyongbela, C. Wirmum, S.M.N. Efange, J. Ethnopharmacol. 114, 452-457 (2007)
17. S.M.N. Efange, R. Brun, S. Wittlin, J.D. Connolly, T.R. Hoye, T. McAkam, F.L. Makolo, J.A. Mbah, D.P. Nelson, K.D. Nyongbela, C.K. Wirmum, J. Nat. Prod. 72, 280-283 (2009)
18. K. Nyongbela, K.I. Ndjoko, R. Brun, S. Wittlin, J. Mbah, F. Makolo, M. Akam, C. Wirmum, S. Efange, K. Hostettmann, Nat. Prod. Comm. 4, 5-8 (2009)
19. K.D. Nyongbela, F.L. Makolo, T.R. Hoye, S.M.N. Efange, Nat. Prod. Commun. 11(1), 5-6 (2016)
20. R.E. Desjardins, C.J. Canfield, J.D. Haynes, J.D. Chulay, Antimicrob. Agents Chemother. 16, 710-718 (1979)
21. R.G. Ridley, W. Hofheinz, H. Matile, C. Jaquet, A. Dorn, R. Masciadri, S. Jolidon, W.F. Richter, A. Guenzi, M.A. Girometta, H. Urwyler, W. Huber, S. Thaithong, W. Peters, Antimicrob. Agents Chemother. 40, 1846-1854 (1996)
22. R.S. Obach, Drug Metab. Dispos. 27(11), 1350-1359 (1999)
23. C.D. Bevan, R.S. Lloyd, Anal. Chem. 72(8), 1781-1787 (2000)
24. F. Lombardo, E. Gifford, M.Y. Shalaeva, Mini. Rev. Med. Chem. 3, 861-875 (2003)
25. F. Lombardo, M.Y. Shalaeva, K.A. Tupper, F. Gao, J. Med. Chem. 44, 2490-2497 (2001)
26. D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, J. Med. Chem. 45, 2615-2623 (2002)
27. R.O. Potts, R.H. Guy, Pharm. Res. 9, 663-669 (1992)
28. R.O. Potts, R.H. Guy, Pharm. Res. 12, 1628-1633 (1995)
29. P.L. Hedley, P. Jorgensen, S. Schlamowitz, R. Wangari, J. Moolman-Smook, P.A. Brink, J.K. Kanters, V.A. Corfield, M. Christiansen, Hum. Mutat. 30, 1486-1511 (2009)
30. J.I. Vandenberg, B.D. Walker, T.J. Campbell, Trends Pharmacol. Sci. 22, 240-246 (2001)
31. N. Chiesa, B. Rosati, A. Arcangeli, M. Olivotto, E. Wanke, J. Physiol. 501, 313-318 (1997)
32. A.M. Aronov, Drug Discov. Today 10, 149-155 (2005)
33. A. Cavalli, E. Poluzzi, F. De Ponti, M. Recanatini, J. Med. Chem. 45, 3844-3853 (2002)
34. F. De Ponti, E. Poluzzi, N. Montanaro, Eur. J. Clin. Pharmacol. 57, 185-209 (2001)
35. F. Ntie-Kang, SpringerPlus 2, 353 (2013)
36. F. Ntie-Kang, J.A. Mbah, L.M. Mbaze, L.L. Lifongo, M. Scharfe, J. Ngo Hanna, F. Cho-Ngwa, P. Amoa Onguéné, L.C. Owono Owono, E. Megnassan, W. Sippl, S.M.N. Efange, BMC Complement Altern. Med. 13, 88 (2013)
37. F. Ntie-Kang, L.L. Lifongo, J.A. Mbah, L.C. Owono Owono, E. Megnassan, L.M. Mbaze, P.N. Judson, W. Sippl, S.M.N. Efange, In Silico Pharmacol. 1, 12 (2013)
38. F. Ntie-Kang, J.A. Mbah, L.L. Lifongo, L.C. Owono Owono, E. Megnassan, L.M. Mbaze, P.N. Judson, W. Sippl, S.M.N. Efange, Org. Med. Chem. Lett. 3, 10 (2013)
39. F. Ntie-Kang, D. Zofou, S.B. Babiaka, R. Meudom, M. Scharfe, L.L. Lifongo, J.A. Mbah, L.M. Mbaze, W. Sippl, S.M.N. Efange, PLoS ONE 8, e78085 (2013)
40. T.A. Halgren, J. Comput. Chem. 17, 490-641 (1996)
41. Schrodinger. LigPrep software, version 2.5. LLC, New York (2011a)
42. Schrodinger. Maestro, version 9.2. LLC, New York (2011b)
43. D. Shivakumar, J. Williams, Y. Wu, W. Damm, J. Shelley, W. Sherman, J. Chem. Theory Comput. 6, 1509-1519 (2010)
44. W.L. Jorgensen, J. Tirado-Rives, J. Am. Chem. Soc. 110(6), 1657-1666 (1988)
45. W.L. Jorgensen, D.S. Maxwell, J. Tirado-Rives, J. Am. Chem. Soc. 118(45), 11225-11236 (1996)
46. Schrodinger. QikProp, version 3.4. LLC, New York, NY (2011c)
47. W.L. Jorgensen, E.M. Duffy, Adv. Drug Deliv. Rev. 54, 355-366 (2002)
48. E.M. Duffy, W.L. Jorgensen, J. Am. Chem. Soc. 122, 2878-2888 (2000)
49. W.L. Jorgensen, E.M. Duffy, Bioorg. Med. Chem. Lett. 10, 1155-1158 (2000)
50. Schrodinger Press. QikProp 3.4 User Manual. LLC, New York, NY (2011)
51. G. Colmenarejo, A. Alvarez-Pedraglio, J.-L. Lavandera, J. Med. Chem. 44, 4370-4378 (2001)
52. J.M. Luco, J. Chem. Inf. Comput. Sci. 39, 396-404 (1999)
53. Ajay, G.W. Bermis, M.A. Murkco, J. Med. Chem. 42, 4942-4951 (1999)
54. J. Kelder, P.D. Grootenhuis, D.M. Bayada, L.P. Delbresine, J.P. Ploemen, Pharm. Res. 16, 1514-1519 (1999)
55. M. Yazdanian, S.L. Glynn, J.L. Wright, A. Hawi, Pharm. Res. 15, 1490-1494 (1998)
56. J.D. Irvine, L. Takahashi, K. Lockhart, J. Cheong, J.W. Tolan, H.E. Selick, J.R. Grove, J. Pharm. Sci. 88, 28-33 (1999)
57. P. Stenberg, U. Norinder, K. Luthman, P. Artursson, J. Med. Chem. 44, 1927-1937 (2001)

[1]	Jindi Lu, Weimin Liang, Yiwei Hu, Xi Zhang, Ping Yu, Meiqun Cai, Danni Xie, Qiong Zhou, Xuefeng Zhou, Yonghong Liu, Junfeng Wang, Jiayin Guo, Lan Tang. Metabolism characterization and toxicity of N-hydap, a marine candidate drug for lung cancer therapy by LC-MS method[J]. 应用天然产物, 2024, 14(4): 33-33.
[2]	Yi-Jie Zhai, Jian-Nan Li, Yu-Qi Gao, Lin-Lin Gao, Da-Cheng Wang, Wen-Bo Han, Jin-Ming Gao. Structurally Diverse Sesquiterpenoids with Anti-neuroinflammatory Activity from the Endolichenic Fungus Cryptomarasmius aucubae[J]. 应用天然产物, 2021, 11(3): 325-332.
[3]	Rong-Hua Yin, Zhen-Zhu Zhao, Xu Ji, Ze-Jun Dong, Zheng-Hui Li, Tao Feng, Ji-Kai Liu. Steroids and Sesquiterpenes From Cultures of the Fungus Phellinus igniarius[J]. 应用天然产物, 2015, 5(1): 17-22.
[4]	Can-Bin Ouyang, Xiao-Man Liu, Qi Liu, Jie Bai, Hou-Yong Li, Yuan Li, Qiu-Xia Wang, Dong-Dong Yan, Lian-Gang Mao, Aocheng Cao, Mei-Xia Guo. Toxicity Assessment of Cadinene Sesquiterpenes from Eupatorium adenophorum in Mice[J]. 应用天然产物, 2015, 5(1): 29-36.
[5]	Zi-Ming Chen, Qiong-Ying Fan, Xia Yin, Xiao-Yan Yang, Zheng-Hui Li, Tao Feng, Ji-Kai Liu. Three New Humulane Sesquiterpenes from Cultures of the Fungus Antrodiella albocinnamomea[J]. 应用天然产物, 2014, 4(4): 207-211.
[6]	Xia YIN, Tao FENG, Zheng-Hui LI, Jia SU, Yan LI, Ning-Hua TAN, Ji-Kai LIU. Chemical investigation on the cultures of the fungus Xylaria carpophila[J]. 应用天然产物, 2011, 1(2): 75-80.

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and Preliminary In Vitro and In Silico DMPK Assessment

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

本文评价