The Sadhukhan Lab @ IIT Palakkad
Department of Chemistry

Structural and functional investigation of natural products for biomedical applications: Natural products have long served as a bedrock of drug discovery. Our group is dedicated to exploring a variety of these molecules and transforming them into potential drug candidates. Our primary focus is on unraveling the molecular mechanisms underlying the diverse biological activities of these compounds, utilizing chemoproteomics as a powerful investigative tool. In addition, we leverage our chemical synthesis platform to structurally modify these molecules, aiming to develop potent inhibitors for various proteins/enzymes involved in the prognosis of a wide range of diseases. Beyond drug discovery, we are also interested in exploring the biomaterial potential of these natural products.

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Development of natural product-inspired as well as synthetic antimicrobial agents against antibiotic-resistant pathogens: Our research group focuses on the development of novel antibacterial agents to combat multidrug-resistant (MDR) bacteria. We harness the therapeutic potential of natural products, particularly plant-derived polyphenols, known for their excellent safety profiles and broad-spectrum bioactivity. In addition to natural compounds, our work extends to the design and synthesis of small molecules and the development of innovative metal-based nanoformulations. Through a multidisciplinary approach, we aim to discover and optimize next-generation antimicrobials to address the global challenge of antibiotic resistance.

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Targeting diabetes through polyphenol-based small molecule inhibitors with multi-target activity: Natural products offer immense structural diversity and serve as a rich source of biologically active compounds. Among them, polyphenols stand out for the wide range of multi-therapeutic effects with low cytotoxicity. However, it has several bottlenecks and is ineffective when used directly as a medication. Diabetes, being a multifactorial disease, a single drug targeting a single biological factor is outdated, and it requires a multi-targeting antidiabetic agent. Our lab hereby focused on exploring the multi-therapeutic potential of polyphenols to overcome the bottlenecks while enhancing their efficacy by structural modifications on them.

 

Chemo-proteomics approaches for drug-target interactions using Click chemistry: Chemo-proteomics combines chemistry and proteomics to study how small molecules, like drugs, interact with proteins in living systems. Our group develops small molecule inhibitors and chemical probes to selectively target and label specific proteins in complex biological samples. We investigate small molecule–protein and protein–protein interactions in cells to understand their roles in cellular pathways and diseases. Using techniques such as mass spectrometry, affinity chromatography, gel electrophoresis, and immunoblotting, we study these interactions at the cellular level. We also design bio-orthogonal probes for natural compounds to uncover their mode of action using Cu(I)-catalyzed alkyne-azide Click chemistry

 

Understanding protein post-translational modifications (PTMs) and their enzymatic regulators for therapeutic applications: Another area where we are actively working is understanding protein post-translational modifications (PTMs) and their enzymatic regulators, with the goal of uncovering insights that can drive the development of new therapeutic strategies. PTMs are closely linked to a range of human diseases, including cardiovascular disorders, diabetes, cancer, and neurodegenerative conditions. Gaining detailed insight into the timing and regulation of these modifications is essential to understand the fundamental biological processes and also for guiding the development of novel therapeutics for serious and life-threatening diseases.

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