| Project Id
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BITSRMIT024B001251
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| Project Detail
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| Project Title
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Development of autophagy targeting nature inspired sipro-compounds as promising anticancer therapy followed by preclinical validation
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| Senior Supervision Team (BITS)
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| Supervisor name and Title
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Prof Balaram Ghosh
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School or Department (or company, if applicable)
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BITS PILANI, HYDERABAD CAMPUS
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Email ID
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balaram@hyderabad.bits-pilani.ac.in
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| URL for more info
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https://universe.bits-pilani.ac.in/Hyderabad/balaram/Profile
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| a) Are you currently supervising a BITS or RMIT HDR student?
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YES
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| Please comment how many you are supervising
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9
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| b) Have you supervised an offshore candidate before?
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YES
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| If no, what support structures do you have in place?
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| If yes, please elaborate
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| Senior Supervision Team (RMIT)
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| Supervisor name and Title
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Dr Subashani Maniam
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School or Department (or company, if applicable)
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STEM
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Email ID
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subashani.maniam@rmit.edu.au
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| URL for more info
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https://www.rmit.edu.au/contact/staff-contacts/academic-staff/m/maniam-dr-subashani
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| a) Are you currently supervising a BITS or RMIT HDR student?
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YES
|
| Please comment how many you are supervising
|
11
|
| b) Have you supervised an offshore candidate before?
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YES
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| If no, what support structures do you have in place?
|
|
| If yes, please elaborate
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I have completed 4 candidates under AcSIR to completion in the past and currently 2 candidates. I have had monthly meeting to keep up to date with their research and have a smooth transition when they arrive in Australia.
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| Other Supervisors (BITS)
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| Supervisor name and Title
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School or Department (or company, if applicable)
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| Phone Number (Optional)
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Email ID
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| URL for more info
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| Other Supervisors (RMIT)
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| Supervisor name and Title
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School or Department (or company, if applicable)
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| Phone Number (Optional)
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Email ID
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| URL for more info
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| Field of Research (For Codes)
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| 340401 | Biologically active molecules | 40.00 |
| 340503 | Organic chemical synthesis | 40.00 |
| 340701 | Computational chemistry | 20.00 |
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| Project Description
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We have established one-pot, 3-component, 1,3-dipolar cycloaddition reaction using a microwave reactor to obtain high yields and rapid syntheses of spiro-compounds. Such compounds are known in nature to have pharmaceutical benefits for various diseases such as Alzheimer’s disease, anti-bacterial and many more. The aim of this project is to
1) Conduct computational screening of small spiro compounds for anti-cancer properties.
2) Synthesize the relevant derivatives using a microwave reactor.
3) Determine the anti-cancer properties of the compounds (in vitro and in vivo).
Thus, this research aims to establish spiro-based simple and rapidly synthesizable small organic compounds as therapeutics for cancer treatment with the ultimate goal of translating scientific findings to actual drug development strategies.
Autophagy in cancer cells is considered a double-edged sword since, in the early stages of tumorigenesis, it may act as a tumor suppressor by degrading potentially harmful agents or damaged organelles, thus avoiding the spread of damage including DNA alterations. However, in advanced stages of tumor development, autophagy is a tumor-promoting mechanism because of its ability to sustain tumor viability in stressful microenvironments. Besides this tumor-promoting activity, autophagy is known to resistance to distinct types of therapy, representing a serious obstacle for successful treatment.
Firstly, screening of small molecules with a spiro core structure will be attempted using various databases targeting several proteins that are involved in the autophagy pathway. Then, the best hits will be explored and expanded, and eventually synthetically prepared using retrosyntheses. Subsequently, biological, pharmacological and therapeutic assessment study in vitro and in vivo will be conducted using standardized protocol for anticancer drug discovery.
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| Project Deliverable/Outcomes
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Natural products have always been rich sources of important therapeutic agents. They have been used in their native form in a wide spectrum of therapeutic applications and have been major sources of molecular inspirations for synthesis of structural analogues of importance. They possess various other health and nutritional benefits with little to no side or aftereffects in most cases. In combination of various databases, molecular engineering of bioactive molecules has become more intuitive.
One of the breakthroughs that will be achieved in this project is the use of novel spiro molecules for anti-cancer activity for autophagy pathway with specific targets of protein. At the ‘concept and discovery stage’, we hypothesized that these molecules would be able to elicit anti-cancer activity with analogues synthesized rapidly in large scale using green synthetic methods. Then, basic and applied research will be conducted to establish the potential of these molecules in vitro and in vivo. With promising results which will substantially prove the basic concept of the research, the next stage in the translational pathway is to establish strategic collaborative research activities to develop pre-clinical studies. This collaboration is anticipated to help establish these activities.
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| Research Impact Themes
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| BETTER HEALTH OUTCOMES | BIOTECHNOLOGY |
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| Which RMIT Sustainable Development Goal (SDG) does your project align to
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GOOD HEALTH AND WELLBEING
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| Which RMIT Enabling Impact Platform (EIP) does your project align to
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BIOMEDICAL AND HEALTH INNOVATION
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| Which RMIT Program code will this project sit under?
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DR229 PhD (AppliedChemistry)
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| Student Capabilities and Qualifications
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Pharmaceutical Science
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Medicinal Chemistry
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Pharmacy
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| Preferred discipline of Student
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| Biochemistry, Bioengineering, Biomaterials, Biotech, Biomed Eng/Sciences, Bioinformatics |
| Chemistry |
| Chemistry, Electrochemistry, Medicinal Chemistry, Coputational Chemistry, Colloids, Surface Chemistry, Catalysis |
| Pharmaceautical Sciences, Pharmacology |
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