Chiranjeev Sharma

Diversification in the synthesis of antimalarial trioxane and tetraoxane analogs

Artemisinin and its semi synthetic analogs have established themselves as effective antimalarial drugs. Since artemisinin is naturally isolated, in short supply and is very expensive to synthesize, extensive research on the discovery of peroxidic antimalarial compounds has intrigued scientists to explore structurally simple yet diverse cyclic peroxides. Consequently, trioxanes and tetraoxanes have been identified as promising candidates for the development of the next generation of antimalarial drugs. To combine the latest synthetic routes and methodologies employed in their synthesis along with earlier reports (dating back to 1899), we present an integrated overview on the diversified synthesis of trioxanes, tetraoxanes and their hybrids.

Versatility of peptide nucleic acids (PNAs): role in chemical biology, drug discovery, and origins of life.

This review briefly discussed nomenclature, synthesis, chemistry, and biophysical properties of a plethora of PNA derivatives reported since the discovery of aegPNA. Different synthetic methods and structural analogs of PNA synthesized till date were also discussed. An insight was gained into various chemical, physical, and biological properties of PNA which make it preferable over all other classes of modified nucleic acid analogs. Thereafter, various approaches with special attention to the practical constraints, characteristics, and inherent drawbacks leading to the delay in the development of PNA as gene therapeutic drug were outlined. An explicit account of the successful application of PNA in different areas of research such as antisense and antigene strategies, diagnostics, molecular probes, and so forth was described along with the current status of PNA as gene therapeutic drug. Further, the plausibility of the existence of PNA and its role in primordial chemistry, that is, origin of life was explored in an endeavor to comprehend the mystery and open up its deepest secrets ever engaging and challenging the human intellect. We finally concluded it with a discussion on the future prospects of PNA technology in the field of therapeutics, diagnostics, and origin of life.

Experimental and theoretical study of intramolecular O⋯O interaction in structurally rigid β-keto carboxylic esters

Here we report the crystal structures of quinolone carboxylate and bisethoxycarbonylvinylaniline derivates containing an O⋯O distance shorter than the sum of their van der Waals radii, which can be ascribed to their steric demand per se, which provide unequivocal evidence of intramolecular 1,5-closed shell type interaction. Theoretical studies including Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbital (NBO) analysis are employed to characterize the nature of the closed shell O⋯O interaction. We found that the lone pair electrons on the interacting oxygens undergo stabilization due to negative hyperconjugation and maintains the otherwise repulsive O⋯O close contact.

Recent Advances in Antimalarial Drug Discovery — Challenges and Opportunities

Malaria drug discovery is a challenging and difficult task due to the unavailability of the vaccine and lack of newer drugs. The most potent artemisinin and its deriva‐ tives, widely used in combination therapies for curing malaria worldwide are also now falling to resistance in some parts of the world. Thus, to combat malaria, new drugs possessing high therapeutic value, minimal toxicity, rapid efficacy and low cost are urgently needed. In this chapter, we will provide an integrated overview on the challenges and opportunities in malaria drug discovery with more emphasis on synthesis of peroxidic antimalarials.