Synthesis and cytotoxicity evaluation of (tetrahydro-beta-carboline)-1,3,5-triazine hybrids as anticancer agents.
A series of tetrahydro-beta-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of racemic compounds 69, 71 and 75, which are selectively cytotoxic towards KB (oral cancer) cell line with IC50 values of 105.8, 664.7 and 122.2 nM, respectively; while their enantiopure forms are less active and not selective. Enantiopure compound 42 showed 2.5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC50 value of 740 nM, also arrests cell cycle in G1 phase and induces apoptosis in MCF7 and MDA MB231 cell lines.
Kumar
Ravi
R
Division of Medicinal & Process Chemistry, Central Drug Research Institute, CSIR, Lucknow 226001, India.
Gupta
Leena
L
Pal
Pooja
P
Khan
Shahnawaz
S
Singh
Neetu
N
Katiyar
Sanjay Babu
SB
Meena
Sanjeev
S
Sarkar
Jayanta
J
Sinha
Sudhir
S
Kanaujiya
Jitendra Kumar
JK
Lochab
Savita
S
Trivedi
Arun Kumar
AK
Chauhan
Prem M S
PM
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000737:chemistry*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D014227:Triazines / Q000737:chemistry*
D000970:Antineoplastic Agents; D002243:Carbolines; D014227:Triazines