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Synthesis and Nanoformulation of Metabolic Modulators: A Strategic Approach towards Cancer Therapy

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Title Synthesis and Nanoformulation of Metabolic
Modulators: A Strategic Approach towards
Cancer Therapy
 
Creator Ghosh, Monisankar
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description The process of drug discovery is at the interface of chemistry and biology and this work primarily focuses on the development of therapeutically important metabolic
modulators to combat cancer. Exclusive feature of the cancer cells include prominent metabolic imbalances that is preeminently aligned with the hallmarks of cancer. The
Warburg phenotype is a characteristic feature of the cancer cells that allows them a functional redundancy to enhance resistance towards apoptosis. Tumor cells undergo
glycolysis for ATP generation rather than utilizing TCA cycle and finally produce lactate in presence of lactate dehydrogenase A (LDH-A) that interconvert pyruvate to
lactate and is seen to be responsible for aggressive cancer outcomes. Therefore, LDH-A might be considered as a potential target in the arena of cancer therapeutics as blocking this enzyme would shut down energy supply and associated anabolic reactions. With this background information, this study was undertaken for the synthesis,
characterization and deciphering the tumoricidal potential of a novel “dual hit” molecule wherein it would compete with NADH and pyruvate to inhibit LDH-A and
selectively initiate apoptosis in the cancer cells, without toxic manifestations.
Another objective of the dissertation work was based on the concept of co-drug.Novel co-drug was derivatized and its PLGA based nanoparticles was conceived to be
developed that would further boost up the potential of the co-drug, highlighting the therapeutic prospectus of the metabolic modulator loaded nanoparticles in the rapidly expanding chapter of cancer therapeutics.
It is a well-established fact that two drugs when added in combination at defined doses can inhibit cancer in a synergistic way by changing the characteristic metabolic
signatures of cancer cells. Realizing the potential that derivatized metabolic modulators can destroy the cancer cells via two different routes, their combination at specific calculated doses was envisioned to mutually mitigate the drawbacks of standard chemotherapeutic regimens, concomitantly underlining the prospectus of metabolic modulators in the clinical setting.
 
Date 2016
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2745/1/THESIS.pdf
Ghosh, Monisankar (2016) Synthesis and Nanoformulation of Metabolic Modulators: A Strategic Approach towards Cancer Therapy. PhD thesis, Jadavpur University.
 
Relation http://www.eprints.iicb.res.in/2745/