2‐Mercaptoquinoline Analogues: A Potent Antileishmanial Agent

Abstract

Leishmaniases are endemic in various countries and parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemist. In order to meet this challenge, a series of 2‐mercaptoquinoline derivatives have been synthesized and docked into the active site of Trypanothione reductase (TryR) enzyme required for redox balance of parasite. These were screened on promastigote and intracellular amastigote stages of L. donovani and found to show high levels of antileishmanial activity together with no cytotoxicity. Some of the synthesized compounds tested here, exhibited very steady and promising leishmanicidal activity against both promastigotes & intracellular amastigotes form, and the observations have been superbly supported by the docking results.

Quinoline: A Promising Scaffold in Recent Antiprotozoal Drug Discovery

“…6-Haloquinoline/quinoline mercaptans with arylacyl motif at 3-position were designed and subsequently investigated towards antileishmanial properties. [23] Compared to Miltefosine with IC 50 values of 4.54 μg/mL and 8.72 μg/mL towards promastigote and amastigote forms respectively, approximately half of the evaluated molecules have expressed higher inhibitory properties (IC 50 = 1.34-3.26 μg/mL) towards the promastigote form of L. donovani. Also, remarkable amastigote inhibitory properties (IC 50 = 1.70-4.09 μg/mL) are observed for the evaluated molecules.…”

“…Pyrimidine framework [22] containing quinoline derivatives are promising drug targets as they have dihydrofolate reductase inhibitory properties. 6‐Haloquinoline/quinoline mercaptans with arylacyl motif at 3‐position were designed and subsequently investigated towards antileishmanial properties [23] . Compared to Miltefosine with IC 50 values of 4.54 μg/mL and 8.72 μg/mL towards promastigote and amastigote forms respectively, approximately half of the evaluated molecules have expressed higher inhibitory properties (IC 50 =1.34–3.26 μg/mL) towards the promastigote form of L. donovani .…”

“…The synthesized molecule was checked for its antileishmanial properties towards various strains. [31] Although the activities displayed are inferior compared to Amphotericin B, compound 53 has elicited remarkable antipromastigote activity (L. [23,26,[29][30] The infected-murine macrophages shown reduced percentage of infection of 14.2 and 18.9 towards L. infantum and L. amazonenesis respectively, comparable with results of Amphotericin B. To check the in vivo therapeutic action of compound 53 on L. amazonensis, experimentally-infected BALB/c mice were inspected for change in parasite load wherein significant reductions (29-59 %) in parasitism are noticed.…”