2. Academic Validation
  3. Synthesis of 1,2,4-triazole-linked urea/thiourea conjugates as cytotoxic and apoptosis inducing agents

Synthesis of 1,2,4-triazole-linked urea/thiourea conjugates as cytotoxic and apoptosis inducing agents

  • Bioorg Med Chem Lett. 2018 Jun 1;28(10):1919-1924. doi: 10.1016/j.bmcl.2018.03.074.
Ramya Tokala 1,  Swarna Bale 2,  Ingle Pavan Janrao 1,  Aluri Vennela 1,  Niggula Praveen Kumar 1,  Kishna Ram Senwar 1,  Chandraiah Godugu 3,  Nagula Shankaraiah 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: chandra.niperhyd@gov.in.
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
PMID: 29657100 DOI: 10.1016/j.bmcl.2018.03.074
Abstract

A new series of 1,2,4-triazole-linked urea and thiourea conjugates have been synthesized and evaluated for their in vitro cytotoxicity against selected human Cancer cell lines namely, breast (MCF-7, MDA-MB-231), lung (A549) prostate (DU145) and one mouse melanoma (B16-F10) cell line and compared with reference drug. The compound 5t showed significant cytotoxicity on MCF-7 breast Cancer cell line with a IC50 value of 7.22 ± 0.47 µM among all the tested compounds. Notably, induction of Apoptosis by compound 5t on MCF-7 cells was evaluated using different staining techniques such as acridine orange/ethidium bromide (AO/EB), annexin V-FITC/PI, and DAPI. Further, clonogenic assay indicates the inhibition of colony formation on MCF-7 cells by compound 5t. Moreover, the flow-cytometric analysis also revealed that compound 5t caused the arrest of cells at G0/G1 phase of cell cycle. In addition, the compounds when tested on normal human cells (L-132) were found to be safer with low cytotoxicity profile.

Keywords

1,2,4-Triazoles; Anticancer; Apoptosis; Flow-cytometry; Thiourea; Urea.

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