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Research Projects of → Biotechnology and Bioinformatics Department

Project Title :
Identification and Charachterisation of secondary metabolites from strains of Actinomycetes sp. isolated from Hirakud Dyke soil and a Gene mining study for the putative genes
Principal Investigator and Affiliation : Dr Smaranika Pattnaik
Co-Investigator and Affiliation :
Funding Agency : Science & Technology Department, Govt. of Odisha
Amount Sanction and Duration : 7.1 Lakhs   -   March, 2014 to March, 2018
Project Proposal :

To date, a wide range of identified antibiotics are produced by the members of the Streptomyces genus, but it is estimated that only 3% has been discovered so far. Antibiotic is a combating weapon. The growing resistance of bacteria towards antibiotics is actually a natural evolutionary response induced by continuous exposure to these drugs. The drop in approved antibacterial agents can be seen in the number of approved compounds for over a couple of decades. The challenge now lies in the investigation on the soil isolated Actinomycetes strains demonstrating pronounced antagonistic activity. Keeping this predicament in mind, this pursuit aims at identifying novel natural drug (s) from the strains of newly isolated Streptomyces sp. against some MDR bacterial strains. One of our goals is to define the drug candidate responsible for antagonistic activity against the bacterial strain of clinical relevance. The research outcome will be utilized for formulation of novel drug which should be cost effective and satisfying the GMP (Good Manufacturing Process). The drug with minimised manufacturing cost may be useful for socio economic backward class of people who lead an underprivileged life style.

Project Title :
Development of synthetic derivatives of natural compound, Noscapine as tubulin binding chemotherapeutic agent and evaluation of its synergistic effect with Taxotere for management of human breast cancer
Principal Investigator and Affiliation : Prof. Pradeep Kumar Naik
Co-Investigator and Affiliation : Prof. Anand M. Ramteke, Dept. of Molecular Biology & Biotechnology Tezpur University, Assam and Prof. Sabita Mohapatra, Dept. of Pharmacology, Veer Surendra Sai Institute of Medical Science and Research, Burla, Sambalpur, Odisha and Dr. Srinivas Kantevari, Principal Scientist, CSIR-Indian Institute of Chemical Technology, Hyderabad
Funding Agency : Department of Biotechnology, Govt. of India
Amount Sanction and Duration : 94 Lakhs   -   January, 2018 to December, 2021
Project Proposal :

Drugs that target microtubules, such as taxols, are important chemotherapeutic drugs in clinical management of breast cancer. However, these drugs are plagued with serious toxicity. Besides patients have developed resistant against taxols, suggesting a need for additional anti microtuble agents that have no side effects. We show that Noscapine (an opium alkaloid, orally-bioavailable anti-cough depressant) and its derivatives have shown (a) to interfere with tubulin without effecting the microtubule organization, (b) inhibits the proliferation of cancer cells of different types and induces apoptotic cell death, (c) binds at a site distinct from paclitaxel binding site on tubulin, (d) in vivo toxicological evaluation fail to reveal any toxicity at 300 and 600 mg/kg body weight and (f) have potent anti tumor activity against solid tumors developed with MCF 7 breast cancer cells at high concentration (~300 mg/kg body weight). It is becoming well-appreciated that a toxic drug at its maximum tolerated dose given intermittently is not necessarily better and there exists an opportunity to reduce its dose levels by using combinatorial regimens of drugs that have either different targets or different binding sites onto the same target. In this project, we aim to rationally design and chemically synthesize promising derivatives of noscapine and subject the compounds to rigorous preclinical evaluation to assess their therapeutic potential by using synergistic dose regime with docetaxel to achieve maximal therapeutic outcomes against breast cancer with minimal toxicity based on in vitro and in vivo assay systems. This will enable us to switch to a ‘metronomic style of chemotherapy’ where the tumor is never allowed to ‘recover’ by chronic administration of low doses of cytotoxic drugs at close, regular intervals with no prolonged drug-free interruptions and thus maximize antitumor outcomes without compromising the quality of life. The completion of this project will provide sufficient preclinical data to obtain the status of an investigational new drug (IND), necessary for moving it from bench to clinic.

Project Title :
Preclinical Efficacy Evaluation of Extremely Promising Novel Noscapinoid: A Tubulin-Binding Agent in the Management of Breast Cancer
Principal Investigator and Affiliation : Prof. Pradeep Kumar Naik
Co-Investigator and Affiliation : Dr. Manas Ranjan Naik, Assistant Professor, Veer Surendra Sai Institute of Medical Science and Research, Burla, Sambalpur, Odisha
Funding Agency : Science & Technology Department, Govt. of Odisha
Amount Sanction and Duration : 8.96 Lakhs   -   September, 2017 to August, 2020
Project Proposal :

Despite significant advances in cancer therapy made over the past several decades, breast cancer remains the leading cause of death among gynecological malignancies in India. Late diagnosis is certainly a major reason why many patients are incurable. Equally problematic are limitations of our current therapeutic armamentarium of anticancer drugs such as taxol, vinca-drugs, estramustine, halaven and ixempra for treatment of localized and metastatic aggressive breast cancers. These drugs are plagued by various debilitating toxicities. In this proposal, we are approaching breast cancer therapy by developing an extremely promising and novel Noscapinoid that is strong enough to kill cancer cells, is non-toxic or tolerably toxic to normal tissues by derivatisation of natural lead compound, Noscapine (an opium alkaloid, non-narcotic, orally available, safe antitussive drug for over 40 years and has low toxicity in humans and mice). The project will also focus on understanding the mechanism of action and anticancer potential (preclinical evaluation in breast cancer cell lines and animal models), and assessment of side effects (in animal models), of the novel agent. Our initial efforts have been quite encouraging in that we have some more effective synthetic derivatives of the lead compound, Noscapine by substituting various functional groups in its scaffold structure. These compounds bind to tubulin and arrests cancer cells in mitosis leading to apoptotic cell death without affecting the normal cells. The current project will follow on this preliminary observation and focuses on enhancing the cell killing potential of Noscapine by developing more promising Noscapinoid and thus maximize therapeutic outcomes without compromising the quality of life.