N-substituted noscapine derivatives as new antiprotozoal agents: Synthesis, antiparasitic activity and molecular docking study

Bioorganic Chemistry
Kosar Babanezhad HarikandeiAhmed Al-Harrasi

Abstract

Novel N-substituted noscapine derivatives were synthesized by a three-component Strecker reaction of cyclic ether of N-nornoscapine with varied aldehydes, in the presence of cyanide ion. Moreover, the corresponding amides were synthesized by the oxidation of cyanide moieties in good yields. The in vitro antiprotozoal activity of the products was also investigated. Interestingly, some analogues did put on display promising antiparasitic activity against Trypanosoma brucei rhodesiense with IC50 values between 2.5 and 10.0 µM and selectivity index (SI) ranged from 0.8 to 13.2. Eight compounds exhibited activity against Plasmodium falciparum K1 strain with IC50 ranging 1.7-6.4 µM, and SI values between 2.8 and 10.5 against L6 rat myoblast cell lines. Molecular docking was carried out on trypanothione reductase (TbTR, PDB ID: 2WOW) and UDP-galactose 4' epimerase (TbUDPGE PDB: 1GY8) as targets for studying the envisaged mechanism of action. Compounds 6j2 and 6b2 displayed excellent docking scores with -8.59 and -8.86 kcal/mol for TbTR and TbUDPGE, respectively.

References

Oct 30, 1992·Journal of Medicinal Chemistry·E CarcellerJ Forn
Jul 6, 2000·British Journal of Plastic Surgery·S S Rayatt, A L Moss
Apr 23, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ifedayo V Ogungbe, William N Setzer
Aug 25, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ronan BatistaAlaíde Braga de Oliveira
Feb 2, 2010·European Journal of Medicinal Chemistry·Cedric S GraebinVera Lucia Eifler-Lima
Aug 1, 2012·PLoS Neglected Tropical Diseases·William N Setzer, Ifedayo V Ogungbe
Oct 12, 2012·ChemMedChem·Aaron J DeBonoPeter J Scammells
Oct 23, 2013·Future Medicinal Chemistry·Lori FerrinsJonathan B Baell
Mar 26, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stefanie ZimmermannMichael Adams
Apr 8, 2014·European Journal of Medicinal Chemistry·Aurora L Carreño OteroVladimir V Kouznetsov
Jul 1, 2014·Journal of Medicinal Chemistry·Lori FerrinsJonathan B Baell
Aug 22, 2014·Journal of Medicinal Chemistry·Janek SzychowskiYoussef L Bennani
Oct 15, 2014·ACS Medicinal Chemistry Letters·Hancheng CaiHarry T Chugani
Mar 27, 2015·Journal of Medicinal Chemistry·Aaron DeBonoPeter J Scammells
Nov 13, 2015·European Journal of Medicinal Chemistry·Pierre DaligauxTâp Ha-Duong
Nov 14, 2015·Bioorganic & Medicinal Chemistry Letters·Wenzhong YanJian Li
Sep 19, 2016·European Journal of Medicinal Chemistry·Ana TejeríaFrancisco Palacios
Sep 14, 2017·Medicinal Research Reviews·Xiao-Fei ShangKuo-Hsiung Lee
Apr 27, 2018·Planta medica·Marzieh TabefamMatthias Hamburger
May 10, 2018·European Journal of Medicinal Chemistry·Michael BerningerUlrike Holzgrabe
Oct 27, 2018·European Journal of Medicinal Chemistry·Anne BouchutJamal Khalife
Feb 25, 2019·European Journal of Medicinal Chemistry·Tania LuthraSubhabrata Sen
May 20, 2019·European Journal of Medicinal Chemistry·Daiane D FerreiraAndre G Tempone

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