Nopol-Based Quinoline Derivatives as Antiplasmodial Agents

Abstract

Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The nopyl-quinolin-8-yl amides (2–4) were moderately active against the asexual blood stage of chloroquine-sensitive strain Pf3D7 but inactive against chloroquine-resistant strains PfK1 and PfNF54. The nopyl-quinolin-4-yl amides and nopyl-quinolin-4-yl-acetates analogs were generally less active on all three strains. Interesting, the presence of a chloro substituent at C7 of the quinoline ring of amide 8 resulted in sub-micromolar EC50 in the PfK1 strain. However, 8 was more than two orders of magnitude less active against Pf3D7 and PfNF54. Overall, the nopyl-quinolin-8-yl amides appear to share similar antimalarial profile (asexual blood-stage) with previously reported 8-aminoquinolines like primaquine. Future work will focus on investigating the moderately active and selective nopyl-quinolin-8-yl amides on the gametocyte or liver stages of Plasmodium falciparum and Plasmodium vivax.

Design, synthesis and antifungal evaluation of novel nopol derivatives as potent laccase inhibitors

“…The key intermediate 2 was synthesized according to the reported method 18 . A solution of nopol ( 1 , 2.20 g, 13.23 mmol) in 20 mL acetone was added to a round‐bottom flask.…”

“…The key intermediate 2 was synthesized according to the reported method. 18 A solution of nopol (1, 2.20 g, 13.23 mmol) in 20 mL acetone was added to a round-bottom flask. The solution was cooled in an ice bath, to which 3.88 M Jones reagent was added dropwise using a dropping funnel for 1 h. The reaction process was monitored by TLC.…”

“…10 ⊎-Pinene, one of the natural monoterpenes obtained from turpentine oil, has been found to show a wide range of bioactivities. [11][12][13][14][15] As downstream products of ⊎-pinene, nopol derivatives also exhibit a variety of biological activities, such as antioxidant, 16 insecticidal, 17,18 and antifungal activities [19][20][21] (Figure 1a). Thus, as a class of potential lead compounds with pronounced activity and structural diversity, nopol derivatives are worthy of further study for pharmaceutical or agrochemical use.…”

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

“…They discovered that nopylquinolin‐8‐yl amides ( 59 ‐ 61 , Figure 18) were ineffective against the chloroquine‐resistant strains Pf K1 and Pf NF54 but somewhat potent against Pf 3D7 strains. Interestingly, compound 62 , a 4‐aminoquinolyl analogue with a 7‐chloroquinolyl moiety, displayed considerably greater potential against Pf K1 strains than Pf 3D7 and Pf NF54 strains [85] …”

Domino Nitro Reduction-Friedländer Heterocyclization for the Preparation of Quinolines

“…Quinolines express a multitude of biological activities and are valuable in the treatment of malaria [21][22][23][24][25][26][27] and other tropical diseases (e.g., Chagas disease, human African trypanosomiasis and leishmaniasis) [28] as well as tuberculosis [29], cancer [30,31] and bacterial infections [32]. Several quinoline-based drugs have been known for many years, while others are more experimental in nature.…”