Synthesis and Evaluation of Antimalarial Activity of Oxygenated 3‐alkylpyridine Marine Alkaloid Analogues

Abstract

A series of new oxygenated analogues of marine 3-alkylpyridine alkaloids were prepared from 3-pyridinepropanol in few steps and in good yields. The key step for the synthesis of these compounds was a Williamson etherification under phase-transfer conditions. All new compounds were evaluated for their antiplasmodial activity and cytotoxicity. A significant reduction in parasitaemia was observed for some of the prepared compounds, and the majority of them exhibited a selectivity index (SI) ranging from 2.78 to 15.58, which suggests that these compounds may be a promising class of substances with antimalarial activity.

Effect of 3‐Alkylpyridine Marine Alkaloid Analogues in Leishmania Species Related to American Cutaneous Leishmaniasis

“…In a recent work, some compounds of this type were assayed against Plasmodium falciparum (20). In this paper, some other analogues were tested against Leishmania species, and the results confirm the potential leishmanicidal activity of oxygenated marine alkaloids analogues.…”

“…Chemistry Compounds 5, 6, 7, 10, 12, 13, and 16 were synthesized as previously reported (20). The synthesis of the new 3-alkylpyridine compounds 8, 9, 11, 14, and 15 is depicted in Scheme 1.…”

“…The compounds with better antipromastigote activity (8 and 9) exhibited a strong toxicity against macrophages. It is interesting to point that these compounds exhibited lower in vitro toxicity against the human lungs fibroblast with IC 50 above 50 lM (20). Data from our laboratory has indicated that peritoneal macrophages are more sensible in vitro assays to several compounds tested, including mercaptopurine derivatives and aminoquinoline derivatives, than cultured macrophages as J744A1 cells lines.…”

“…Column chromatography was performed with silica gel 60, 70-230 mesh (Merck). Compounds 5,6,7,10,12,13, and 16 were synthesized as previously reported (20). The new salts 8, 9, 11, 14, and 15 were prepared and characterized as described below.…”

Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

“…Although different classes of metabolites have been isolated from this group of marine sponges, these compounds are typically highlighted for their remarkable cytotoxic activity against tumor human cell lines [11,12], as are their analogs [14]. A small series of 3-APA analogs of theonelladine C (Figure 1) recently synthesized by our research group exhibited antiprotozoal activity [15,16] and pro-apoptotic action against a human colon carcinoma (RKO-AS-45-1) cell line [14]. We also observed that their cytotoxicity appeared to be affected by the alkyl chain length (9 or 12 carbon atoms) and the type of functional group attached to the end of this chain (e.g., azide or amine) (Figure 1).…”