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Quinoline, a privileged scaffold in medicinal chemistry, has always been associated with a multitude of biological activities. Especially in antimalarial and anticancer research, quinoline played (and still plays) a central role, giving rise to the development of an array of quinoline-containing pharmaceuticals in these therapeutic areas. However, both diseases still affect millions of people every year, pointing to the necessity of new therapies. Quinolines have a long-standing history as antimalarial agents, but established quinoline-containing antimalarial drugs are now facing widespread resistance of the Plasmodium parasite. Nevertheless, as evidenced by a massive number of recent literature contributions, they are still of great value for future developments in this field. On the other hand, the number of currently approved anticancer drugs containing a quinoline scaffold are limited, but a strong increase and interest in quinoline compounds as potential anticancer agents can be seen in the last few years. In this review, a literature overview of recent contributions made by quinoline-containing compounds as potent antimalarial or anticancer agents is provided, covering publications between 2018 and 2020., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The parasitic disease malaria places almost half of the world's population at risk of infection and is responsible for more than 400,000 deaths each year. The first-line treatment, artemisinin combination therapies (ACT) regimen, is under threat due to emerging resistance of Plasmodium falciparum strains in e.g. the Mekong delta. Therefore, the development of new antimalarial agents is crucial in order to circumvent the growing resistance. Chloroquine, the long-established antimalarial drug, still serves as model compound for the design of new quinoline analogues, resulting in numerous new active derivatives against chloroquine-resistant P. falciparum strains over the past twenty years. In this work, a set of functionalized quinoline analogues, decorated with a modified piperidine-containing side chain, was synthesized. Both amino- and (aminomethyl)quinolines were prepared, resulting in a total of 18 novel quinoline-piperidine conjugates representing four different chemical series. Evaluation of their in vitro antiplasmodium activity against a CQ-sensitive (NF54) and a CQ-resistant (K1) strain of P. falciparum unveiled highly potent activities in the nanomolar range against both strains for five 4-aminoquinoline derivatives. Moreover, no cytotoxicity was observed for all active compounds at the maximum concentration tested. These five new aminoquinoline hit structures are therefore of considerable value for antimalarial research and have the potency to be transformed into novel antimalarial agents upon further hit-to-lead optimization studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The tropical disease malaria is responsible for more than 400,000 deaths annually, especially in Southeast Asia and Africa. Although the number of malaria cases is declining, there still is an urgent need for novel antimalarial agents. The emergence of hybrid antimalarial agents and the precedence set by the antimalarial drug ferroquine (FQ) prompted us to design new ferrocene-containing quinoline structures. Herein, we report the efficient synthesis of three different series of ferrocene-quinoline conjugates and a class of ferrocene-containing heterotricycles in good to high yields. For all twenty novel ferrocenyl derivatives, electrochemical properties were investigated using cyclic voltammetry and antiplasmodium evaluation against a chloroquine-susceptible NF54 strain of the human malaria parasite Plasmodium falciparum was conducted, pointing to three compounds showing submicromolar potency. Subsequently, cytotoxicity assays against a Chinese Hamster Ovarian cell line and evaluation against a chloroquine-resistant strain of Plasmodium falciparum for these three compounds revealed selective and promising antiplasmodium activity., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)