Cancer needs no introduction. The dreaded disease has claimed millions of lives throughout the world. Despite being actively studied across the globe, a possible cure for cancer remains elusive. Treatment is usually given in the form of chemotherapy, which is associated with a lot of side effects. Most of the drugs which are given with the intention to kill cancerous cells, can also kill normal cells in the body.
Developing new drugs which are potent at much lower concentrations is essential to minimize side effects. Researchers at the Indian Institute of Science in collaboration with KLE University’s College of Pharmacy, Bangalore; Singhania University, Rajasthan; Institute of Bioinformatics and Applied Biotechnology, Bangalore and Rega Institute for Medical Research, Belgium have synthesized organic compounds that can be used in extremely small concentrations as potential anti-cancer agents.
Several chemical compounds display anti-cancer properties. Organic compounds like hydrazide derivatives and acyclic thiosemicarbazones are two such examples.
In an earlier study, the same group had reported another compound – a thiosemicarbazide derivative – as a cytotoxic agent. These agents have a half maximal inhibitory concentration (IC50) of 2300 nM. That is, the compound inhibits biological processes in the cells by half, at a concentration of 2300 nM. Nanomolar is a unit of concentration that measures how much of a substance is in solution.
This study was undertaken with the aim of developing anti-cancer agents which could function at a much lower IC50 value. The compounds that were synthesized were N’-[2-oxo-1,2 dihydro-3H-indol-3-ylidene] benzohydrazides with an IC50 value of 660 nM. These compounds were then tested for their cytotoxic activity on human cervix carcinoma grown on a plate (HeLa cells), T-cells which are important immune cells in the body, and on another cancer cell line L1210 cells.
The mechanism of action of these potent anti-cancer drugs was also elucidated using two cancer cell lines, REH and K562. REH is a pre-B cell leukemia cell line whereas K562 is a chronic myeloid leukemia cell line. Both these cell lines have originated from humans and thus were appropriately used for the aforementioned study. The anti-cancer properties of these derivatives could be attributed to the induction of apoptosis or programmed cell death without arresting the normal cell cycle.
Preliminary studies indicate that these benzohydrazides show potent anti-cancer activities and are effective at much lower concentrations (nanomoles compared to micromoles) for most drugs. Further studies would enable the development of these compounds as promising anti- cancer candidates for clinical trials.
About the authors
The paper is a multi-country, multi-institutional collaboration, between Department of Biochemistry, Indian Institute of Science, Bangalore, Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore, Department of Pharmacy and Medical Science, Singhania University, Rajasthan, India, Institute of Bioinformatics and Applied Biotechnology, Electronics City, Bangalore, India and the Rega Institute for Medical Research, Belgium.
Subhas Karki. E-mail: email@example.com; Fax: +91 080 23425373; Tel: +91 080 23325611
Sathees Raghavan. http://biochem.iisc.ernet.in/scraghavan.php
Tel: +91-80-2293 2674; Email: firstname.lastname@example.org
About the study:
The paper appeared in the journal RSC Advances on 13th May. http://pubs.rsc.org/en/Content/ArticleLanding/2015/RA/c5ra01528f#!divAbs...