Microwave-assisted synthesis of sec/tert-butyl 2-arylbenzimidazoles and their unexpected antiproliferative activity towards ER negative breast cancer cells.
A new series of N-sec/tert-butyl 2-arylbenzimidazole derivatives was synthesised in 85-96% yields within 2-3.5 min by condensing ethyl 3-amino-4-butylamino benzoate with various substituted metabisulfite adducts of benzaldehyde under focused microwave irradiation. The benzimidazole analogues were characterised using (1)H NMR, (13)C NMR, high resolution MS and melting points. Evaluation of antiproliferative activity of the benzimidazole analogues against MCF-7 and MDA-MB-231 revealed several compounds with unexpected selective inhibitions of MDA-MB-231 in micromolar range. All analogues were found inactive towards MCF-7. The most potent inhibition against MDA-MB-231 human breast cancer cell line came from the unsubstituted 2-phenylbenzimidazole 10a.
School of Pharmaceutical Sciences, Universiti Sains Malaysia , Penang , Malaysia.
Aisyah Saad
AS
Abdul Rahim
Salizawati Muhamad
SM
Salhimi
Natarajan
N
Arumugam
Lim Chung
LC
Pin
Ng Shy
NS
Yee
Nithya Niranjini
NN
Muttiah
Wong Boon
WB
Keat
Shafida
S
Abd Hamid
Hasnah
H
Osman
Ishak b
Ib
Mat
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008872:Microwaves; D015394:Molecular Structure; D011960:Receptors, Estrogen; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D011960:Receptors, Estrogen; C031000:benzimidazole