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Total Synthesis, Antileishmanial and Anticancer Activity of the Acetylenic Fatty acids 6‐Hexadecynoic, 10‐Phenyl‐6‐decynoic, and 10‐Cyclohexyl‐6‐decynoic Acids
Author(s) -
Álvarez Ester,
Carballeira Néstor,
Morales Christian,
Delgado Yamixa,
Tinoco Arthur,
Reguera Rosa,
Álvarez Raquel,
Balaña Rafael
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.608.7
Subject(s) - cytotoxicity , leishmania infantum , leishmania donovani , a549 cell , biochemistry , chemistry , visceral leishmaniasis , leishmania , biology , pharmacology , apoptosis , leishmaniasis , immunology , in vitro , parasite hosting , world wide web , computer science
Naturally occurring acetylenic fatty acids have been recognized for their biological activity towards cancer and protozoal parasites. Lung cancer is one of the deadliest types of cancer and the second most incidental cancer in both men and women. Previous research has shown that these acids display cytotoxicity against the human lung carcinoma cell line A549. On the other hand, leishmaniasis is a neglected disease caused by the protozoan parasite Leishmania donovani(infantum) that affects mostly underdeveloped countries and can be fatal in the most severe cases (visceral leishmaniasis). Our laboratory has shown that the Δ6 alkynoic fatty acids display antiprotozoal activity and inhibit the Leishmania donovani topoisomerase IB enzyme ( Ld TopIB). In this work, the total syntheses of the naturally occurring 6‐hexadecynoic acid and the synthetic 10‐phenyl‐6‐decynoic and 10‐cyclohexyl‐6‐decynoic acids were completed in 5 steps (67–77% overall yields). The 6‐hexadecynoic acid displayed good inhibition of Ld TopIB (EC‐‐ 50 =61 μM) and cytotoxicity towards L. infantum iRFP70 promastigotes (IC 50 =100 μM). In addition, the 6‐hexadecynoic acid also displayed cytotoxicity towards the human lung A549 cell line (EC‐ 50 = 65 μM). On the other hand, the 10‐phenyl‐6‐decynoic acid did not inhibit Ld TopIB (EC‐‐ 50 >200 μM) and displayed no cytotoxicity towards L. infantum iRFP70 promastigotes (IC 50 >100 μM) as well as no cytotoxicity towards A549 (EC 50 >100 μM) . The 10‐cyclohexyl‐6‐decynoic acid also showed no inhibition of Ld TopIB, no cytotoxicity towards L. infantum promastigotes, but displayed cytotoxicity against the A549 cell line (EC‐ 50 = 87 μM). Our results show that the 6‐hexadecynoic acid was the best of the series due to its inhibitory activity towards Ld TopIB and toxicity towards L. infantum promastigotes and the A549 cell line. Support or Funding Information NIH‐MARC Program undergraduate fellowship (5T34GM00781‐37) and the NIH‐RISE Program graduate fellowship (5R25GM061151‐15)