2-(3-Aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: A New Antileishmanial Chemotype

Abstract

A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI50 < 1 microM) as well as on parasites in infected macrophages.

Insect Antifeedant Potent Halogen Substituted Phenyl Chalcones

“…The AVATAR-300 Fourier transform spectrophotometer was used for recording infrared spectra (KBr, 4000-400 cm -1 ) of all chalcones in KBr disc. The Bruker AV400 series type NMR spectrometer was utilized for recording NMR spectra of all chalcones, operating at 400MHz for 1 H and 100 MHz for 13 C spectra in CDCl 3 solvent using TMS as internal standard. Mass spectra of all synthesised chalcones were recorded on SHIMADZU mass spectrometer using chemical ionization technique.…”

“…Numerous chalcone derivatives are used as agrochemicals [1] and drugs [2] due to their structurally important multipronged activities by the presence of carbonyl, vinyl and polar substituents in their structure. The important multipronged activities of chalcones are antimicrobial [3], anti-cancer [4], anti-viral [5], anti-malarial [6], anti-oxidant [7], antiproliferative [8], anti-AIDS [9], anti-tuberculosis [10], anti-plasmodial [11], antiinflammatory [12], anti-leshmanial [13], anti-convulsant [14], cytotoxic [15], anti-parasitic [16], anti-angiogenic [17], anti-mycobacterial [13], anti-trichomonal [19], anti-amastigote [20], radio protective [21], and insect antifeedant activities [22].…”

2-tert-Butyl-5,6,7,8,9,10-hexahydrocyclohepta[b]indole

“…. Recently paullone chalcone hybrid structures 1 were reported to inhibit the growth of Leishmania amastigotes in vitro [7]. In order to study structure-activity relationships regarding this antiparasitic activity congeners related to 1 are currently investigated.…”

“…Abstract: 2-tert- 6,7,8,9,indole was synthesized by reaction of cycloheptanone and (4-tert-butylphenyl)hydrazine hydrochloride in the presence of sodium acetate and sulfuric acid in glacial acetic acid via Fischer indole synthesis. .…”

“…Among other biological properties, paullones have demonstrated antiproliferative activity on cancer cell lines on the one hand [1][2][3][4][5] and protection of insulin producing pancreatic beta cells against apoptosis on the other hand [6]. Recently paullone chalcone hybrid structures 1 were reported to inhibit the growth of Leishmania amastigotes in vitro [7]. In order to study structure-activity relationships regarding this antiparasitic activity congeners related to 1 are currently investigated.…”