Anti-malarial, cytotoxicity and molecular docking studies of quinoline Based Chalcones

Abstract

Chalcone is among the key compounds of natural products that is widely circulated throughout plant kingdoms like tea, vegetables and fruits. Chalcones has recently become a matter of great attention to researchers in their medicinal activities. Some of the main therapeutic activity related with chalcones comprise: anti-inflammatory, antitumor activities, anti-HIV, antifungal, antioxidant, anti-tuberculosis, analgesic and antimalarial anticancer antiviral. The chalcones are separated from various portions of plants including blossoms, roots, seeds, flowers, leaves, and buds during 1960‟s and 70‟s. The chalcones present in plants in combined state as well as in free State, either as a glycoside (linked with carbohydrate) or as a free chalcones. Herein, 14 quinolinyl chalcones (A1-A14) are synthesized by the condensation of chloro and methyl substituted formyl quinoline with various substituted phenyl and hetero-aromatic ketones. The precursors (formyl quinoline) are synthesized via Vilsmeier Haack reaction of acetanilide, that in turn are prepared through N-acetylation of aniline in the presence of CH3COOH and O phosphoric acid. Finally, all of the synthesized compounds (14 compounds in number) are screened for biological activities such as anti-HIV-1, antimalarial, cytotoxicity activities and heme bindings. Many of the prepared quinolinyl chalcones were proved to be potent biologically active compounds. The computational and molecular docking studies of all quinolinyl chalcones were also performed. The molecular docking and theoretical results were consistent with experimental results. The anti-HIV and anti-malarial activities depends upon the type and position of substituent attached to the quinolinyl chalcones. The experimental and theoretical studies illustrated that the quinolinyl chalcones with electron withdrawing groups (e.g. Cl, Br) were more active against HIV and malarial parasites as compared to electron donating groups containing quinolinyl chalcones. According to molecular docking and theoretical studies the electron withdrawing groups were more hydrophobic in nature, so they Institute of Chemistry, University of the Punjab, Lahore Page xviii can easily enter the cell via crossing the lipophilic cell membrane. Moreover, the electron withdrawing group attached at less sterically hinder position are more biologically active as compared to the same electron withdrawing substituent attached at sterically hinder position.