ascorbic-acid and quinoline

Indoloquinoline (IQ) is an important class of naturally occurring antimalarial alkaloids, mainly represented by cryptolepine, isocryptolepine, and neocryptolepine. The IQ structural framework consists of four isomeric ring systems differing via the linkage of indole with quinoline as [3,2-b], [3,2-c], [2,3-c], and [2,3-b]. Structurally, IQs are planar and thus they bind strongly to the DNA which largely contributes to their biological properties. The structural rigidity and associated nonspecific cellular toxicity is a key shortcoming of the IQ structural framework for preclinical development. Thus, the lead optimization efforts were aimed at improving the therapeutic window and ADME properties of IQs. The structural modifications mainly involved attaching the basic aminoalkyl chains that positively modulates the vital physicochemical and topological parameters, thereby improves biological activity. Our analysis has found that the aminoalkylation consistently improved the selectivity index and provided acceptable in-vivo antimalarial/anticancer activity. Herein, we critically review the role of aminoalkylation in deciphering the antimalarial and cytotoxic activity of IQs.

Topics: Alkaloids; Antimalarials; Antineoplastic Agents; Cell Proliferation; Indoles; Malaria; Molecular Structure; Neoplasms; Quinolines

A series of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives 4a(1)-4n(2) were designed and synthesized based on the 2-oxo-quinoline structure core as novel antioxidants. In vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants ascorbic acid, BHT and BHA, employing DPPH() assay, ABTS(+) assay, O(2)(-) assay and OH() assay. The results showed that IC(50) of most compounds were lower than standard value 10mg/mL, indicating good antioxidant activities of these compounds. In addition, in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 4b(2), 4e(1), 4e(2) and 4g(2), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) cation (ABTS(+)) radical scavenging activities of compounds 4a(1), 4e(1), 4e(2), 4f(1), 4f(2), 4g(1), 4g(2), 4h(1), 4h(2), 4k(1), 4k(2), 4n(1) and 4n(2), superoxide anion radical scavenging activities of 4b(1), 4e(1), 4f(2), 4j(1), 4k(1), 4k(2), 4m(1), 4m(2), and 4n(2), and hydroxyl radical scavenging activity of almost all the compounds except 4f(1), 4f(2), 4j(2), 4l(1) and 4l(2) were better than that of the commercial antioxidant butylated hydroxytoluene (BHT).

Topics: Antioxidants; Hydroxyl Radical; Quinolines; Schiff Bases; Superoxides