88858-79-1Relevant academic research and scientific papers
Design and synthesis of potent antitumor water-soluble phenyl N-mustard-benzenealkylamide conjugates via a bioisostere approach
Tala, Satishkumar D.,Ou, Tai-Hsin,Lin, Yi-Wen,Tala, Kiranben S.,Chao, Shu-Hsin,Wu, Ming-Hsi,Tsai, Tung-Hu,Kakadiya, Rajesh,Suman, Sharda,Chen, Ching-Huang,Lee, Te-Chang,Su, Tsann-Long
, p. 155 - 169 (2014/03/21)
A series of new, water-soluble phenyl N-mustard-benzenealkylamide conjugates containing hydrophilic ω-dialkylaminoalkylamide or ω-cyclic aminoalkylamide moieties were synthesized via a bioisostere approach. These compounds have a broad spectrum of antitumor activity against a panel of human tumor cell lines. Of these derivatives, compound 18b effectively suppressed the growth of colon cancer (HCT-116), prostate cancer (PC3), and lung cancer (H460) xenografts. The growth of HCT-116 xenografts was almost completely suppressed when co-treated with compound 18b and 5-fluorouracil. Furthermore, compound 18b can induce DNA cross-linking and cell-cycle arrest at the G2/M phase. Early preclinical studies, including pharmacokinetics in rats, inhibition of the hERG, and 14 days of acute intravenous injection toxicity, suggest that compound 18b is a promising candidate for further preclinical studies.
A novel series of G-quadruplex ligands with selectivity for HIF-expressing osteosarcoma and renal cancer cell lines
Lombardo, Caterina M.,Welsh, Sarah J.,Strauss, Sandra J.,Dale, Aaron G.,Todd, Alan K.,Nanjunda, Rupesh,Wilson, W. David,Neidle, Stephen
supporting information, p. 5984 - 5988 (2012/11/07)
A series of naphthalene derivatives with disubstituted triazole side-arms have been assembled by click chemistry. Lead compounds show a high level of selectivity for renal, osteo- and Ewing's sarcomas that express the HIF-1α transcription factor. They also interact selectively with the quadruplex DNAs located in the promoter of the HIF genes and it is suggested that the mechanism of action involves inhibition of transcription by drug-mediated quadruplex stabilization in these regions.
Structure-based design of selective high-affinity telomeric quadruplex-binding ligands
Lombardo, Caterina Maria,Martinez, Iria Sanchez,Haider, Shozeb,Gabelica, Valerie,De Pauw, Edwin,Moses, John E.,Neidle, Stephen
supporting information; experimental part, p. 9116 - 9118 (2011/02/23)
A library of triazole-based telomeric quadruplex-selective ligands has been developed that mimic an established family of tri-substituted acridine-based ligands, using crystal structure data as a starting-point for computer-based design. Binding affinities, estimated by electrospray mass spectrometry, are in accord with the design concept.
