Shahabuddin, M. S. ; Nambiar, Mridula ; Advirao, Gopal M. ; Raghavan, Sathees C. (2011) Intercalative pyrimido[4',5':4,5]thieno(2,3-b)quinolines induce apoptosis in leukemic cells: a comparative study of methoxy and morpholino substitution Investigational New Drugs, 29 (5). pp. 873-882. ISSN 0167-6997
Full text not available from this repository.
Official URL: http://link.springer.com/article/10.1007%2Fs10637-...
Abstract
DNA intercalating molecules are promising anticancer agents. Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and affect major physiological functions. In the present study, we have characterized two molecules with the same chemical backbone but different side chains, namely 8-methoxy pyrimido[4',5':4,5]thieno (2,3-b)quinoline-4(3H)-one (MPTQ) and 4-morpholino pyrimido[4',5':4,5]thieno(2,3-b)quinoline (morpho-PTQ) at the 8th and 4th position, respectively. Although both MPTQ and morpho-PTQ show similar biophysical properties with high DNA affinity, here we show that they differ in their biological activities. We find that MPTQ is many fold more potent than morpho-PTQ and is cytotoxic against different leukemic cell lines. IC50 value of methoxy PTQ was estimated between 2-15 µM among the leukemic cells studied, while it was more than 200µM when morpho-PTQ was used. Cell cycle analysis shows an increase in sub-G1 phase, without any particular cell cycle arrest. Annexin V staining in conjunction with comet assay and DNA fragmentation suggest that MPTQ induces cytotoxicity by activating apoptosis. Thus the observed low IC50 value of MPTQ makes it a promising cancer chemotherapeutic agent.
Item Type: | Article |
---|---|
Source: | Copyright of this article belongs to Springer Verlag. |
Keywords: | Chemotherapy;Double-strand Breaks;Cytotoxicity;DNA Damage; Anticancer Drug |
ID Code: | 104150 |
Deposited On: | 07 Apr 2017 06:32 |
Last Modified: | 01 Feb 2018 10:11 |
Repository Staff Only: item control page