Antileishmanial Ring-Substituted Ether Phospholipids

Abstract

Three series of ring-substituted ether phospholipids were synthesized carrying N,N,N-trimethylammonium, N-methylpiperidino, or N-methylmorpholino headgroups. The first series is substituted by 2-cyclohexyloxyethyl or 2-(4-alkylidenecyclohexyloxy)ethyl groups, the second series by cyclohexylidenealkyl or adamantylidenealkyl moieties, and the third series by 2-aryloxyethyl or 6-aryloxyhexyl groups in the alkyl portion of the molecule. The antileishmanial activity of the new compounds was evaluated in vitro against the promastigote forms of L. donovani and L. infantum using an MTT (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide)-based microassay as a marker of cell viability. Analogues 12, 15, 24, 30, 32, 41, 43, and 45 were more potent than the control compound miltefosine (hexadecylphosphocholine) against both L. donovani and L. infantum while, derivatives 13 and 42 were equipotent to miltefosine. Analogues 16, 17, 19, 20 were more potent than miltefosine against L. infantumand compounds 27, 31, 44 were more active than miltefosine against L. donovani. Differential scanning calorimetry (DSC) was used to probe the role of individual ether phospholipids on the physicochemical properties of model membranes. The DSC scans showed that the active compounds have a more profound effect on the thermotropic properties of model membrane bilayers than the less active ones.

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

“…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.…”

“…In addition, miltefosine failed to treat the American species related to ACL (11). As a result, new drugs for the treatment of leishmaniasis still require improvement (12).…”

Synthesis of simple molecules prepared as arginase inhibitors and evaluated against Leishmania amazonensis

“…There are many species of the protozoa that can infect humans and are responsible for the following main forms of leishmaniasis (Ashford, 2000;Avlonitis et al, 2003;Croft et al, 2003): cutaneous, mucocutaneous, diffuse cutaneous and visceral leishmaniasis. Cutaneous leishmaniasis (CL) is caused by Leishmania major and mucocutaneous leishmaniasis (ML) is caused by Leishmania braziliensis and generates sores on the skin.…”

“…These drugs are also very toxic and administered parenterally (Avlonitis et al, 2003;Croft et al, 2003;Guerin et al, 2002). Due to the increasing number of published reports on drug resistance and toxicity, as well as the occurrence of Leishmania/HIV co-infection, there is an urgent need to search for alternative therapies.…”

In Silico Analyses of Epicoccamides on Selected Leishmania Trypanothione Reductase Enzyme-based Target

“…There are many species of the Leishmania that can infect humans and are responsible for the following different forms of leishmaniasis: mucocutaneous, cutaneous, visceral and diffuse cutaneous leishmaniasis [2][3][4] . Mucocutaneous leishmaniasis (ML) is caused by Leishmania braziliensis and its prognosis is sores on the skin while cutaneous leishmaniasis (CL) is caused by L. major.…”