Assistant professor, Sam higginbottom university of agriculture technology and sciences (SHUATS)
Pharmaceutical chemist looking for novel molecules for anti virulence therapeutics.
Dr. Bhatia is a medicinal chemist with strong focus on the theoretical and synthetic medicinal chemistry. Her work involves rational drug design approach to synthesize compounds of medicinal interest. Her research work flow involves the use of (i) Quantum chemical methods to design compounds for the target proteins (basically anti-virulence targets) (ii) Use of CADD approaches (QSAR, Mol. Dock., mol. Dynamics, etc.) to design new entities (iii) Synthesis of computationally designed species (iv) Biologically evaluation of anti-virulence compounds on the Multi-Drug Resistant (MDR) strains of pathogenic bacteria. Along with this she also works on novel non remote carbenic species which can act a ligand in the complexes of main group elements. The group in which she was working has recently identified a novel class of nitrogen species with divalent N(I) state and labelled them as nitreones. Nitreones are low valent nitrogen species (Chem. Eur. J. 2016, 22, 1088; J. Org. Chem. 2014, 79, 4852-486, J. Phys. Chem. A, 2012, 116, 9071; J. Comp. Chem. 2013, 34, 1577) in which the central nitrogen (i) is found in the low oxidation state N(I), (ii) carries two lone pairs of electrons, (iii) forms coordination bonds with electron donating groups like carbenes (iv) isoelectronic to the newly identified carbones, carbon compounds with C(0) oxidation state and (v) low nucloephilicity of nitreones makes them useful as drugs. The main focus of her Ph.D. thesis was to identify and analyse the scaffolds which are therapeutically important and can show novel divalent N(I) character. In this scenario, drugs like famotidine and ebrotidine were identified to possess divalent N(I) character.(J. Phys. Chem. A, 2012, 116, 9071). In addition to this she has also identified several stereo-electronic descriptors which are responsible for governing the chemical reactivity of divalent N(I) systems (J. Org. Chem. 2014, 79, 4852-486). Through the use of combine quantum and molecular mechanics approach she identified the biguanide framework which can have potential to inhibit quorum sensing proteins, which is further synthesized and analysed using biological assays. (Med. Chem. Res. 2015, 24, 1974-1987). Research work of the Dr. Bhatia in collaborative projects in theoretical organic chemistry and organometallic chemistry also yielded significant results (Tetrahedron 2013, 69, 10284-10291; J. Mass Spectrometry, 2014, 49, 452-467).
Abstract: The great clinical significance of biofilm-associated infections and their inherent recalcitrance to antibiotic treatment urgently demand the development of novel antibiofilm strategies. In this regard, antimicrobial peptides (AMPs) are increasingly recognized as a promising template for the development of antibiofilm drugs. Indeed, owing to their main mechanism of action, which relies on the permeabilization of bacterial membranes, AMPs exhibit a strong antimicrobial activity also against multidrug-resistant bacteria and slow-growing or dormant biofilm-forming cells and are less prone to induce resistance compared to current antibiotics. Furthermore, the antimicrobial potency of AMPs can be highly increased by combining them with conventional (antibiotics) as well as unconventional bioactive molecules. Combination treatments appear particularly attractive in the case of biofilms since the heterogeneous nature of these microbial communities requires to target cells in different metabolic states (e.g., actively growing cells, dormant cells) and environmental conditions (e.g., acidic pH, lack of oxygen or nutrients). Therefore, the combination of different bioactive molecules acting against distinct biofilm components has the potential to facilitate biofilm control and/or eradication. The aim of this review is to highlight the most promising combination strategies developed so far to enhance the therapeutic potential of AMPs against bacterial biofilms. The rationale behind and beneficial outcomes of using AMPs in combination with conventional antibiotics, compounds capable of disaggregating the extracellular matrix, inhibitors of signaling pathways involved in biofilm formation (i.e., quorum sensing), and other peptide-based molecules will be presented and discussed.
Pub.: 30 Jan '18, Pinned: 09 Feb '18
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