Synthesis, antimalarial activities and cytotoxicities of amino-artemisinin-1,2-disubstituted ferrocene hybrids.

Bioorganic & Medicinal Chemistry Letters
Christo de LangeDavid D N'da

Abstract

Artemisinin-ferrocene conjugates incorporating a 1,2-disubstituted ferrocene analogous to that embedded in ferroquine but attached via a piperazine linker to C10 of the artemisinin were prepared from the piperazine artemisinin derivative, and activities were evaluated against asexual blood stages of chloroquine (CQ) sensitive NF54 and CQ resistant K1 and W2 strains of Plasmodium falciparum (Pf). The most active was the morpholino derivative 5 with IC50 of 0.86 nM against Pf K1 and 1.4 nM against Pf W2. The resistance indices were superior to those of current clinical artemisinins. Notably, the compounds were active against Pf NF54 early and late blood stage gametocytes - these exerted >86% inhibition at 1 µM against both stages; they are thus appreciably more active than methylene blue (∼57% inhibition at 1 µM) against late stage gametocytes. The data portends transmission blocking activity. Cytotoxicity was determined against human embryonic kidney cells (Hek293), while human malignant melanoma cells (A375) were used to assess their antitumor activity.

Citations

May 27, 2020·Chemistry : a European Journal·Prinessa Chellan, Peter J Sadler
Apr 17, 2020·Frontiers in Pharmacology·Ming XiaHong Liu
Oct 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sibusiso Alven, Blessing Aderibigbe
Dec 12, 2018·European Journal of Medicinal Chemistry·Chuan GaoLian-Shun Feng
Jan 29, 2021·European Journal of Medicinal Chemistry·Om P S PatelLesetja J Legoabe
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mziyanda MbabaSetshaba D Khanye
Nov 19, 2021·Journal of Medicinal Chemistry·Bharvi Sharma, Vipan Kumar

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