Soumita Mukherjee

Quinolines: a new hope against inflammation.

Although a number of anti-inflammatory drugs have been discovered and developed to treat diseases associated with acute and chronic inflammation, many anti-inflammatories cause adverse side effects. The quinoline framework has emerged as a new template for the design and identification of novel anti-inflammatory agents. These agents are classified based on the number of substituents present on the quinoline ring or compounds containing a quinoline ring fused to other heterocycles. This review focuses on the discovery of various quinoline derivatives as inhibitors of cyclooxygenase (COX), phosphodiesterase 4 (PDE4) and tumour necrosis factor-α converting enzyme (TACE), along with transient receptor potential vanilloid 1 (TRPV1) antagonists.

Novel N-indolylmethyl substituted olanzapine derivatives: their design, synthesis and evaluation as PDE4B inhibitors

A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.

Ligand/PTC-free intramolecular Heck reaction: synthesis of pyrroloquinoxalines and their evaluation against PDE4/luciferase/oral cancer cell growth in vitro and zebrafish in vivo

A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.

Cu-catalyzed coupling-cyclization in PEG 400 under ultrasound: a highly selective and greener approach towards isocoumarins

The combination of CuI–K2CO3-PEG 400 facilitated the coupling-cyclization of o-iodobenzoic acid with terminal alkynes under ultrasound, affording a greener and practical approach towards 3-substituted isocoumarins with remarkable regioselectivity. This inexpensive and Pd and ligand free methodology gave rise to various isocoumarins of potential pharmacological interest.

Zebrafish based strategy for the identification of a potential pharmacophore for apoptosis: a greener CuAAC approach for novel 1,2,3-triazoles derived from mefenamic acid

Prompted by the potential of a screening strategy in zebrafish for the identification of valuable pharmacophores, a series of triazole substituted mefenamic acid derivatives were designed and synthesized via a CuAAC under green conditions. A variety of terminal alkynes were reacted with the azide obtained from mefenamic acid to give the expected products in good to excellent yields. When screened for apoptosis, teratogenicity and hepatotoxicity in zebrafish embryos, one of these compounds showed encouraging apoptotic properties and safety profiles and seemed to have medicinal value.