2. Academic Validation
  3. Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies

Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies

  • Eur J Med Chem. 2017 Jan 27:126:24-35. doi: 10.1016/j.ejmech.2016.09.093.
Prinka Singla 1,  Vijay Luxami 2,  Raja Singh 3,  Vibha Tandon 3,  Kamaldeep Paul 4
Affiliations

Affiliations

  • 1 School of Chemistry and Biochemistry, Thapar University, Patiala, 147004, India.
  • 2 School of Chemistry and Biochemistry, Thapar University, Patiala, 147004, India. Electronic address: vluxami@thapar.edu.
  • 3 Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110 067, India.
  • 4 School of Chemistry and Biochemistry, Thapar University, Patiala, 147004, India. Electronic address: kpaul@thapar.edu.
PMID: 27744184 DOI: 10.1016/j.ejmech.2016.09.093
Abstract

A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human Cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum Anticancer activities at 10 μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50 values of 1.30 μM, 1.43 μM, 2.38 μM and 2.18 μM, respectively against several Cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce Apoptosis and inhibit human Topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).

Keywords

Antitumor activity; Benzimidazole; Bovine serum albumin; Pyrazolo[3,4-d]pyrimidine; ct-DNA.

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