Application of PEG400 in the one-pot synthesis of 7-[4-alkyl- or (hetero)aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines via SNAr and Cu(I)-Catalyzed Azide-Alkyne Cycloaddition and preliminary evaluation of their anti-tumour activity

Abstract

Several novel 7-[4-alkyl-or (hetero)aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines were prepared in good to high yields, using the environmentally friendly solvent PEG 400 in a one-pot procedure from 7chlorothieno[3,2-b]pyridine to form the corresponding azide via S N Ar with NaN 3 , followed by Cu(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) using different types of alkynes. This one-pot reaction in PEG 400 starting from a halogenated heteroaromatic system is reported for the first time and demonstrated a wide scope of application for alkynes. Preliminary anti-tumour activity on human tumour cell lines using the prepared 1,4-di(hetero)aryl-1,2,3-triazoles was evaluated, together with their toxicity in non-tumour cells. Among the tested compounds the most promising one was a 2-ethynylpyridine derivative.

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy

“…In this work, a novel antitumor compound, a thieno[3,2- b ]pyridine derivative ( Figure 1 ), was encapsulated in magnetoliposomes containing multicore manganese ferrite nanoparticles. This compound has shown promising antitumor activity at very low growth inhibitory concentrations (GI 50 ) in four human tumor cell lines, namely, HeLa (cervical carcinoma; GI 50 =12.99 ± 0.58 µM), MCF-7 (breast adenocarcinoma; GI 50 =15.13 ± 0.59 µM), NCI-H460 (non-small cell lung carcinoma; GI 50 = 12.60 ± 0.8 µM) and HepG2 (hepatocellular carcinoma; GI 50 = 7.51 ± 0.48 µM) [ 17 ], being especially active against hepatocellular carcinoma. Moreover, the compound has shown a much lower cytotoxic effect in non-tumor cells PLP2 (Porcine Liver Primary cells; GI 50 = 91.94 ± 5.23 µM) [ 17 ], thus being promising as a chemotherapeutic agent, with no predicted negative impact in normal tissues.…”

Magnetoliposomes Containing Multicore Nanoparticles and a New Thienopyridine Antitumor Compound for Chemo/Thermotherapy

“…The fluorescent antitumor thienopyridine derivative was previously synthesized [12]. The UV-Visible absorption and fluorescence spectra were measured in several solvents with different polarities and results are shown in figure 12.…”

“…In this work, a novel antitumor compound, a thieno [3,2-b]pyridine derivative (figure 1), was encapsulated in magnetoliposomes containing multicore manganese ferrite nanoparticles. This compound has shown a promising antitumor activity with low growth inhibitory concentrations (GI50) in four tumor cell lines, namely in HeLa (cervical carcinoma; GI50 =12.99 ± 0.58 µM), MCF-7 (breast adenocarcinoma; GI50 =15.13 ± 0.59 µM), NCI-H460 (non-small cell lung carcinoma; GI50 = 12.60 ± 0.8 µM) and HepG2 (hepatocellular carcinoma; GI50 = 7.51 ± 0.48 µM) [12]. Moreover, the compound has shown a much lower cytotoxic effect in non-tumor cells PLP2 (Porcine Liver Primary cell line; GI50 = 95.94 ± 5.23 µM), being thus promising as a chemotherapeutic agent [12].…”

“…This compound has shown a promising antitumor activity with low growth inhibitory concentrations (GI50) in four tumor cell lines, namely in HeLa (cervical carcinoma; GI50 =12.99 ± 0.58 µM), MCF-7 (breast adenocarcinoma; GI50 =15.13 ± 0.59 µM), NCI-H460 (non-small cell lung carcinoma; GI50 = 12.60 ± 0.8 µM) and HepG2 (hepatocellular carcinoma; GI50 = 7.51 ± 0.48 µM) [12]. Moreover, the compound has shown a much lower cytotoxic effect in non-tumor cells PLP2 (Porcine Liver Primary cell line; GI50 = 95.94 ± 5.23 µM), being thus promising as a chemotherapeutic agent [12]. With the motivation of achieving more effective and synergistic therapies through the combination of magnetic hyperthermia and chemotherapy, reducing the drug dosage needed by application of a local treatment, the nanosystems were evaluated for their potential of drug release and magnetic hyperthermia capabilities.…”