Inhibition of Human Tumor Cell Proliferation by the Telomerase Inhibitor TELIN

Abstract

Summary TELIN, a newly developed catalytic blocker of telomerase, was assessed for its antiproliferative activity against human tumor cells in in vitro cell culture assay. TELIN suppressed cell proliferations of several blood tumor cells with telomere shortening and the appearance of apoptotic small cells, but did not affect hTERT mRNA expression, suggesting that TELIN catalytically inhibited telomerase activity within the cells. TELIN also suppressed cell proliferation of adherent tumor cells, whereas it did not affect the growth of normal fibroblasts. Delivery efficiency of TELIN was significantly different between several delivery carriers, and b-cyclodextrin was found to be a suitable carrier.

4-Disubstituted Pyrazolin-3-Ones—Novel Class of Fungicides against Phytopathogenic Fungi

“…Most of the previously known biologically active C4-disubstituted pyrazolones, with the exception of TELIN [43], belong to the class of spiro compounds bearing two C-C bonds at C4. Thus, the main structural feature that distinguishes the pyrazolones tested by us from other biologically active C4-disubstituted pyrazolones is the presence of a C4-heteroatom bond, which may be a key aspect for the manifestation of fungicidal activity.…”

“…Due to the wide spectrum of the biological activity of disubstituted pyrazolones, new asymmetric methods for their synthesis are being actively developed [36][37][38][39][40][41]. C4-disubstituted pyrazolones are recognized as valuable antitumor agents [35,[42][43][44][45][46], antimicrobial substances [47], inhibitors of trypanosomal phosphodiesterase B1 [48], RalA inhibitors [49], and miticides [50]. However, their potential as effective fungicides has not been expected.…”

Highly Site‐ and Enantioselective N—H Functionalization of N‐Monosubstituted Aniline Derivatives Affording Pyrazolones Bearing a Quaternary Stereocenter

“…As an important five‐membered nitrogen heterocycles, [ 1 ] pyrazolones have attracted much attention for the wide application in medicinal, pharmaceutical, agrochemical or coordination chemistry fields. [ 2 ] Additionally, 4,4‐disubstituted pyrazolones as a common scaffold, exist in a wide range of biologically active compounds (Figure 1), such as compound A with tolomerase activity, [ 3 ] compound B with analgesic activity, [ 4 ] compound C with RaIA activity. [ 5 ] So the asymmetric synthesis of pyrazolones bearing a quaternary stereocenter at 4 position has become an attractive goal and many efficient synthetic approaches have been established over the past years.…”

Squaramide-catalyzed asymmetric regioselective allylic alkylation of 4-aminopyrazolones with Morita–Baylis–Hillman carbonates

“…Pyrazolone, one of the core five-membered heterocycles, is often found in bioactive molecules and pharmaceuticals. 3 For example, compound A shows an analgesic effect, 4 Telin ( B ) is an antineoplastic agent, 5 and WS9326H ( C ), 6 a new cyclic peptide isolated from a mudflat derived streptomyces strain, exhibits anti-angiogenesis property (Fig. 1).…”