Excitement surrounds the identification of a new chemical entity with anticancer properties through DBT’s mission programme on microbial prospecting.
Prospecting of drugs from microbes through public-private partnership is the first of its kind academia-industry alliance project which targets the microbial biodiversity from different environmental niches. The nine academia partners and Piramal Life Sciences Limited (PLSL), Mumbai are involved in this study with the support of Department of Biotechnology for screening microbes for drug development.
The nine academia partners and Piramal Life Sciences Limited (PLSL), Mumbai are involved in this study with the support of Department of Biotechnology for screening microbes for drug development. The project envisages a mega scale screening programme for various environmental isolates. This is the first project in the country where industry and academia will work together to screen such a large number of bacterial isolates.
Through this programme, nearly 250000 microbes from niche areas were screened on high throughput screening platforms on four different therapeutic areas namely cancer, diabetes, inflammation and anti-infectives. Based on the screening on four different therapeutic areas, nearly 16000 Hits have been identified and these have been set aside for future studies for the isolation of novel scaffolds from them.
This screening program was designed carefully by selecting academic groups that could supply to the program pure cultures of microbes isolated from different niches across India. The microbial laboratories selected for this purpose were experts in their domain area. The concept was selecting such microbes from these niche areas may lead us to study some previously unexplored microbes. From the magnitude of the study this appears to one of the largest screening programs in the country which has now created a large offshoot of microbial collection for use for any sort of screening ventures. The screening of microbial natural products continues to represent an important route to the discovery of novel bioactive and therapeutic chemicals. The project envisages a mega scale screening programme for various environmental isolates.
With these assets in hand, it was decided to move into the next phase to pinpoint the actual molecules that may be responsible for the therapeutic action. In the next phase, 1000 extracts that were taken up potent for the different bioactivity in study were into the next round of investigation referred to as chemical characterization.The second phase of activities involves chemical characterization of selected 1000 three star hits. The activities will be shared between NEERI, Nagpur and Piramal Life Sciences Limited, Mumbai.
The outcome of this program has been phenomenal with One New Chemical Entity with anticancer and anti-inflammatory activity and 12 probable new use of compound were identified for which one US patent “Use of a thiopeptide compound in the treatment of Clostridium difficile associated infections” has been filed and a PCT application claiming priority from the US provisional application related to use of Micrococcin P1 for the treatment of Clostridium difficile infections has been filed and few are under process.A catalogue of 133 compounds (51 purified compounds and 82 Postulated structures) has been prepared mentioning the bioactivity and all other details of the microbes and also classifications.
As part of the Microbial Mission programme, Department has established the Microbial Culture Collection Centre (MCC) in the country at the National Centre for Cell Science (NCCS), Pune to maintain the 2,00,000 isolates generated under this project. This is the largest such facility in the country and received ‘International Depositary Authority (IDA)’ recognition which from April 9, 2011. It also acquired the status of ‘Designated Repository’ under the Biodiversity Act, 2002 in July 2013. This repository is the focal point for storage of Microbial cultures collected under the Microbial Mission Programme. MCC is also carrying out the task of characterizing and preserving nations’ precious microbial diversity. The centre has so far described 15 novel bacteria from diverse ecological habitats, 14 new species and two genera were described first time in the world.
At present efforts are being made to explore the strategies for moving some of the active molecules obtained in the current program from discovery to Pre- Investigational New Drug (IND) studies, thereby creating a path of development of molecules.
It can save a lot of time in this globally competitive area of R & D in the area of drug discovery. Natural Products (NP) based drug discovery was dropped by many big Pharma as they adapted to drug discovery through a chemistry approach such as combinatorial chemistry. Mainly due to NP research was time consuming, faced lot of reiteration and long drawn process although earlier, Natural Products was thought to be a source of novel scaffolds. However, there has been a comeback to harness natural products to obtain scaffolds for drug research, as the pipelines are dry in the global Pharma industry. However, the automation in chemistry and the process to predict whether an extract has a novel entity by dereliction has rekindled interest in the area.