Saturday, 2 April 2011

Anti-cancer drugs: IICT designs novel pyrrolo-benzo-diazepine molecules

2010
By Syed Akbar
Hyderabad, June 8: The city-based Indian Institute of Chemical Technology has designed novel pyrrolo-benzo-diazepine (PBD) molecules that will pave the way for safe anti-cancer drugs.
These molecules serve as potential DNA-binding agents with enhanced anti-tumour activity. "They have shown good DNA binding affinity with better anti cancer activity," says IICT director grade scientist Dr Ahmed Kamal.
These molecules have been tested against 60 human cancer cell lines derived from nine cancer types. Among them one analogue exhibited significant activity against 41 cell lines.
"A major limitation of cancer chemotherapy results from the lack of tumour specificity shown by most anti cancer drugs leading to severe side-effects due to the destruction of healthy tissues. One approach to overcome these drawbacks is the development of relatively non-toxic anti cancer agents, in a prodrug (relatively less active) form, specifically activated in and around the tumour tissue," he said.
An ideal prodrug needs to be stable inside the body (in vivo), far less toxic than its parent form, and activated specifically in or within the micro environment of the tumour cells or tumour site. "In this laboratory, PBD prodrugs containing a Ggalactoside moiety have been synthesised for application in selective chemotherapy of cancer. They possess all the essential requirements for their potential
application in targeted therapy of cancer by enzyme directed therapies. The in vivo targeting ability of the prodrugs is being initiated," Dr Kamal said.
Despite the availability of anti cancer agents derived from natural products and their semisynthetic derivatives, the development of a safe and site-specific anti cancer drug still remains a challenge.
The major obstacles for this challenge are the association of toxicity with drugs which is due to lack of specificity, as these agents kill healthy cells and the drug resistance which have arisen in recent years.
According to Dr Kamal, the combination therapy employing different chemotherapeutic agents has been used to combat this problem with some success. However, the possibility of the development of drug resistance still remains.
The IICT has now focused its efforts towards the intervention of site-specific anti cancer agents eventually to develop effective chemotherapeutics for the treatment of human malignancies, he said.

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