Hologram QSAR Studies of Antiprotozoal Activities of Sesquiterpene Lactones

Molecules

Gustavo H. G. Trossini¹  Vinໜius G. Maltarollo¹ 

[1] Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Lineu Prestes, 580, 05508-000 São Paulo, Brazil; E-Mail:

关键词: HQSAR;    sesquiterpene lactones;    Trypanosoma brucei;    Trypanosoma cruzi;    Leishmania donovani;    Plasmodium falciparum;    antiprotozoal activity;    fragment-based drug design;   

DOI  :  10.3390/molecules190710546

来源: mdpi

【 摘 要 】

Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural products such as sesquiterpene lactones have shown activity against T. brucei and L. donovani, the parasites responsible for these neglected diseases. To evaluate structure activity relationships, HQSAR models were constructed to relate a series of 40 sesquiterpene lactones (STLs) with activity against T. brucei, T. cruzi, L. donovani and P. falciparum and also with their cytotoxicity. All constructed models showed good internal (leave-one-out q² values ranging from 0.637 to 0.775) and external validation coefficients (r²_test values ranging from 0.653 to 0.944). From HQSAR contribution maps, several differences between the most and least potent compounds were found. The fragment contribution of PLS-generated models confirmed the results of previous QSAR studies that the presence of α,β-unsatured carbonyl groups is fundamental to biological activity. QSAR models for the activity of these compounds against T. cruzi, L. donovani and P. falciparum are reported here for the first time. The constructed HQSAR models are suitable to predict the activity of untested STLs.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.