Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring

Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery.

Nickel (II) complexes of naphthaquinone thiosemicarbazone and semicarbazone: synthesis, structure, spectroscopy, and biological activity.

Spectral characterization, cyclic voltammetry, morphology, biological activities and DNA cleaving studies of amino acid Schiff base metal(II) complexes

Synthesis, characterization, and spectroscopic studies of tetradentate Schiff base chromium(III) complexes

Metal complexes of a new thiosemicarbazone derived from 3-acetylumbelliferone (HL) have been prepared and characterized. The complexes have the general formula ML2 · nH2O where MII = Co, Ni, Cu and Zn; n = 0 and 2. The ligand and its complexes have been studied for their possible antitumour activity against HL-60 human leukemia in vitro.

Antitumour activity of transition metal complexes with the thiosemicarbazone derived from 3-acetylumbelliferone

The PI3K/Akt/mTOR pathway is frequently dysregulated in cancer due to its central role in cell growth, survival, and proliferation. Overactivation of the PI3K/Akt/mTOR pathway may occur through varying mechanisms including mutations, gene amplification, and upstream signaling events, ultimately resulting in cancer. Therefore, PI3K/Akt/mTOR pathway has emerged as an attractive target for cancer therapy and imaging. A promising approach to inhibit this pathway involves a simultaneous inhibition of both PI3K and mTOR using a dual inhibitor. Recently, a potent dual PI3K/mTOR inhibitor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (7), was discovered and demonstrated excellent kinase selectivity IC50 (PI3K/mTOR) = 0.20/21 nM; good cellular growth inhibition IC50 (HCT-116 cell) = 10 nM, modest plasma clearance, and acceptable oral bioavailability. Expanding on this discovery, here we present the synthesis of the carbon-11 labeled imidazo[1,2-a]pyridine derivative 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-[11C]methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (N-[11C]7) as a new potential radiotracer for the biomedical imaging technique positron emission tomography (PET) imaging of PI3K/mTOR in cancer. The reference standard 7 and its N-demethylated precursor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(piperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (11), were synthesized in 7 and 8 steps with 10% and 7% overall chemical yield, respectively. N-[11C]7 was prepared from 11 using [11C]methyl triflate ([11C]CH3OTf) through N-11C-methylation and isolated by high-performance liquid chromatography (HPLC) and solid-phase extraction (SPE) formulation in 40-50% radiochemical yield decay corrected to end of bombardment (EOB) based on [11C]CO2. The radiochemical purity was > 99% and the molar activity (Am) at EOB was in the range of 296-555 GBq/µmol (n = 5).

Zhi-Dong Xu

Papers

Antitumour activity of transition metal complexes with the thiosemicarbazone derived from 3-acetylumbelliferone

A carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET probe targeting PI3K/mTOR in cancer.