Geeta M. Kulkarni

Recent advances in coumarins and 1-azacoumarins as versatile biodynamic agents

Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring lactones and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early days, have now been extensively studied for their biological activities. These investigations have revealed their potentials as versatile biodynamic agents. For example, coumarins with phenolic hydroxyl groups have the ability to scavenge reactive oxygen species and thus prevent the formation of 5-HETE and HHT in the arachidonic pathway of inflammation suppression. Recent in vivo studies have revealed the role of coumarins in hepatotoxicity and also in depletion of cytochrome P450. Similarly 1-azacoumarins which is part of quinoline alkaloids, are known for their diverse biological activity and recently, a 6-functionalized 1-aza coumarins are undergoing human clinical trials as an orally active anti-tumor drug in view of its farnesyl protein-inhibiting activity in the nanomolar range. Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for anti-microbial, anti-HIV, anti-cancer, lipid-lowering, anti-oxidant, and anti-coagulation activities. Specifically, coumarin-3-sulfonamides and carboxamides were reported to exhibit selective cytotoxicity against mammalian cancer cell lines. The C4-substituted aryloxymethyl, arylaminomethyl, and dichloroacetamidomethyl coumarins, along with the corresponding 1-azacoumarins, have been demonstrated to be potential anti-microbial and anti-inflammatory agents. To expand the structural diversity of synthetic courmarins for biological functions, attempts have also been made to attach a chloramphenicol side chain at C-3 position of courmarin. In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models. Photobiological studies on pyridine-fused polycyclic coumarins have highlighted their potential as thymine dimer photosensitisers and the structurally related compounds of both coumarin and carbostyrils have also been found to act via the DNA gyrase pathway in their anti-bacterial activity. Apart from the above works, the present review also addresses the potential roles of coumarins and carbostyrils as protease inhibitors, or fluorescent probes in mechanistic investigation of biochemical pathways, and their application for QSAR in theoretical studies. Though 1-Azacoumarins have received less attention as compared to coumarins in the literature, an attempt has been made to compare both the systems at various stages, so that it can spark new thoughts on synthetic methodologies, reactivity pattern and biological activities.

Synthesis and biological studies of some new acrylic acid ethyl esters of quinolinone

A series of new acrylic acid ethyl esters of quinolinones were synthesized from 4-(bromomethyl)quinolinones and screened for in vitro antimicrobial and in vivo analgesic and anti-inflammatory activities. Most of the compounds with chloro substitution at the C-6 or C-7 position in the quinolinone moiety and a methoxy group in the aryloxy moiety showed potent antibacterial and antifungal activities when compared with non-halogenated quinolinones and the quinolinones bearing a CH3 at the C-8 position. In a pharmacological evaluation, the halogen substitution at the C-6 or C-7 position in quinolinones was found to enhance both analgesic and anti-inflammatory activities of the molecule when compared with a simple unsubstituted (non-halogenated) quinolinone. The structures of all newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, and FAB-MS.Graphical abstract

N-(2-Chloro­quinolin-3-ylmethyl­ene)aniline

The title compound, C16H11ClN2, displays a trans configuration across the C=N bond and a transoid arrangement across the quinoline ring and the azomethine C atom. This arrangement facilitates C—H⋯Cl interactions. The packing in the crystal structure is due to intermolecular C—H⋯π and Cl⋯π (3.52 and 3.84 Å) interactions. The dihedral angle between the least-squares planes of 2-chloroquinoline and phenylamine is 16.61 (2)°.

8-[(Hydrazinyl-idene)meth-yl]-4-methyl-2-oxo-2H-chromen-7-yl 4-methyl-benzene-sulfonate.

In the title compound, C18H16N2O5S, the coumarin ring system is nearly planar, with a maximum out-of-plane deviation of 0.078 (1) Å (r.m.s. deviation = 0.046 Å). The dihedral angle between the coumarin ring system and the toluene ring (r.m.s. deviation = 0.004 Å) is 2.77 (1)°. The crystal packing is stabilized by C—H⋯O and N—H⋯O intermolecular hydrogen bonds generating C(8), C(9) and C(11) chains and R 2 2(14), R 2 2(23) and R 4 3(13) ring graph sets.

Synthetic and biological studies on mono- and bis-methylene-bridged heterocyclic sulfides and sulfones of carbostyrils

A series of new sulfides and sulfones of carbostyrils were synthesized and tested for their in vitro antimicrobial and in vivo analgesic activities. The results of a bioassay showed that these newly synthesized compounds exhibit potential antibacterial and antifungal activities. The chloro substitution at C-6 and C-7 positions of carbostyrils was found to enhance the antimicrobial activity. Similarly, halogen-substituted sulfones were found to possess potent analgesic activities. All the newly synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, ESI-MS and FAB-MS.

New, Efficient, Selective, and One-Pot Method for Acylation of Amines

Abstract Hydrazine hydrate with acetic and propionic acids was an efficient reagent for acylation of primary and secondary amines at reflux temperatures. The reported one-pot method is high-yielding, simple, mild, and inexpensive.

8-Formyl-4-methyl-2-oxo-2H-chromen-7-yl 4-methyl­benzenesulfonate

In the title compound, C18H14O6S, the coumarin ring system is nearly planar, with a maximum out-of-plane deviation of 0.032 (2) Å. The dihedral angle between the benzene ring and the coumarin ring system is 32.41 (8)°. The crystal packing is stabilized by intermolecular C—H⋯O interactions, generating C(8), C(10) and C(11) chains and an R 2 2(10) ring. The formyl group is disordered over two sets of sites, with occupancies of 0.548 (5) and 0.452 (5).