The pinene scaffold: its occurrence, chemistry, synthetic utility, and pharmacological importance.

Plant-based secondary metabolites have been a major source of drug discovery and inspiration for new generations of drugs. Plants offer a wide variety of compound classes, including alkaloids, terpenes, flavonoids, and glycosides, with different molecular architectures (fused bridgehead, bi- and polycyclic, spirocyclic, polycyclic, and acyclic). The diversity, abundance, and accessibility of plant metabolites make plants an attractive source of human and animal medicine. Even though the pinene scaffold is abundant in nature and has historical use in traditional medicine, pinene and pinene-derived compounds have not been comprehensively studied for medicinal applications. This review provides insight into the utility of the pinene scaffold as a crucial building block of important natural and synthetic products and as a chiral reagent in the asymmetric synthesis of important compounds.

Nopol-Based Quinoline Derivatives as Antiplasmodial Agents.

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.