Abstract:
:A series of 2-(3-aryl-2-propenoyl)-3-methylquinoxaline-1,4-dioxides 3a-l were prepared by condensation of various aryl aldehydes with 2-acetyl-3-methylquinoxaline-1,4-dioxide 2. These compounds inhibit the growth of human Molt 4/C8 and CEM T-lymphocytes and the IC(50) values are mainly in the 5-30 microM range. The quinoxaline 1,4-dioxide 3j inhibited the growth of 58 human tumor cell lines, particularly leukemic and breast cancer neoplasms. All of the compounds 3a-l reversed the multidrug resistance (MDR) properties of murine L-5178Y leukemic cells which were transfected with the human MDR1 gene. The MDR-reversing effect may be due to the conjugated pi-electron system forming a weak electron charge transfer complex with the P-glycoprotein-mediated efflux pump. The compounds in series 2 and 3 were assessed against HL-60, HSC-2, HSC-3 and HSC-4 malignant cells as well as HGF, HPC and HPLF normal cell lines which revealed that the majority of the compounds displayed a greater toxicity to neoplastic than normal cells. Various ways in which the project may be expanded are presented.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Das U,Pati HN,Panda AK,De Clercq E,Balzarini J,Molnár J,Baráth Z,Ocsovszki I,Kawase M,Zhou L,Sakagami H,Dimmock JRdoi
10.1016/j.bmc.2009.04.021subject
Has Abstractpub_date
2009-06-01 00:00:00pages
3909-15issue
11eissn
0968-0896issn
1464-3391pii
S0968-0896(09)00367-8journal_volume
17pub_type
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