Jayabal Kamalraja

Synthesis, characterization and biological evaluation of chromen and pyrano chromen-5-one derivatives impregnated into a novel collagen based scaffold for tissue engineering applications

In this article, we describe the synthesis and biological evaluation of a novel 2-(methylamino)-3-nitro-4-(4-oxo-4H-chromen-3-yl) pyrano[3,2-c]chromen-5(4H)-one (CCN). It is also determined that CCN impregnated into the collagen scaffold has the potential to mimic the function of the extracellular matrix as a biomaterial in the field of tissue engineering. The series of pyrano[3,2-c]chromen-5(4H)-one derivatives (4a–4j), was analyzed by 1H NMR, 13C NMR, mass spectra and FTIR analysis. Compound 4c was confirmed by single crystal XRD studies. All the compounds were screened for antimicrobial activity against Gram positive, Gram negative bacteria and yeast. Among all the compounds, compound (4aCCN) showed activity against Gram positive and Gram negative bacteria, when compared to the synthesized compounds. Further, compound CCN was evaluated for cytotoxicity against MCF-7, Hep-2 and Vero cancer cell lines with IC50 values of 5.4 μg ml−1, 5.3 μg ml−1 and 68.4 μg ml−1 respectively. In addition, the results of flow cytometry and docking (PDBID: 1A27 with the ligand) studies supported the activity of the synthesized compound (4a). FTIR and NMR analysis of the CCN impregnated collagen scaffold were done to reveal the existence of the CCN molecule in the scaffold. The inherent property of the collagen scaffold was not significantly affected by the structure of the CCN molecule. The thermal and mechanical properties of the collagen scaffold impregnated with CCN molecules gives stability as well as supports the swelling. However, the COL-CCN scaffold showed an enhanced cell attachment and proliferation of NIH 3T3 fibroblast cells. Based on the results, the novel CCN molecule impregnated within a collagen scaffold has potential application as a biomaterial in tissue engineering.

InCl3-mediated eco-friendly three-component domino reaction for synthesis of highly functionalized triazolylspiroxindolinopyrans and triazolylpyrans under solvent-free conditions

A one pot domino protocol has been developed for the efficient synthesis of novel triazolylspiroxindolinopyrans and triazolylpyran derivatives. The synthesis was achieved by reacting phenacyltriazole, isatin/aromatic aldehyde and active methylene compounds in the presence of InCl3 under solvent-free conditions at 100 °C. This novel strategy affording biologically relevant heterocyclic compounds presumably involves Knoevenagel condensation/Michael addition/6-exo-dig-cyclisation sequences.

4-(4-Bromo-phen-yl)-7,7-dimethyl-2-methyl-amino-3-nitro-7,8-di-hydro-4H-chromen-5(6H)-one including an unknown solvate.

In the title compound, C18H19BrN2O4, the chromene unit is not quite planar (r.m.s. deviation = 0.199 Å), with the methyl C atoms lying 0.027 (4) and 1.929 (4) Å from the mean plane of the chromene unit. The six-membered carbocyclic ring of the chromene moiety adopts an envelope conformation, with the dimethyl-substituted C atom as the flap. The methylamine and nitro groups are slightly twisted from the chromene moiety, with C—N—C—O and O—N—C—C torsion angles of 2.7 (4) and −0.4 (4)°, respectively. The dihedral angle between the mean plane of the chromene unit and the benzene ring is 85.61 (13)°. An intramolecular N—H⋯O hydrogen bond generates an S(6) ring motif, which stabilizes the molecular conformation. In the crystal, molecules are linked via N—H⋯O hydrogen bonds, forming hexagonal rings lying parallel to the ab plane. A region of disordered electron density, most probably disordered ethanol solvent molecules, occupying voids of ca 432 Å3 for an electron count of 158, was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148–155]. Their formula mass and unit-cell characteristics were not taken into account during refinement.

2-Amino-6-(pyrrolidin-1-yl)-4-p-tolyl­pyridine-3,5-dicarbonitrile

In the title compound, C18H17N5, the pyrrolidine ring adopts an envelope conformation. The pyrrolidine ring is disordered over two sets of sites with occupancy factors of 0.648 (6) and 0.352 (6). The dihedral angles between the pyrrolidine and pyridine rings are 14.6 (3)° for the major component and 16.2 (6)° for the ninor component. The crystal structure is stabilized by intermolecular N—H⋯N and C—H⋯N interactions.

rac-4-(4-Chloro-phen-yl)-2-methyl-amino-3-nitro-5,6,7,8-tetra-hydro-4H-chromen-5-one.

The title compound, C16H15ClN2O4, contains a chiral centre and crystallizes as a racemate. The methylene group β-positioned to the carbonyl group is partially (21%) disordered. It flips to the opposite sides of the corresponding six-membered carbocycle by −0.304 (3) and 0.197 (11) Å, producing alternative envelope conformations. The planes of the pyran and chlorophenyl rings form a dihedral angle of 86.25 (9)°. The molecular structure is characterized by an intramolecular N—H⋯O interaction, which generates an S(6) ring motif. The corresponding amino N atom deviates from the plane of the pyran ring by 0.1634 (19) Å. In the crystal, molecules are linked via C—H⋯O hydrogen bonds, forming C(8) chains running parallel to the b-axis direction. The crystal structure also features C—H⋯π interactions.

Crystal structure of 1'-(prop-2-yn-1-yl)-1,4-di-hydro-spiro-[benzo[d][1,3]oxazine-2,3'-indolin]-2'-one.

In the title compound, C18H14N2O2, the six-membered oxazine ring adopts a half-chair conformation and its mean plane makes a dihedral angle of 83.23 (7)° with the pyrrolidine ring of the indoline ring system. In the crystal, molecules are linked via N—H⋯O hydrogen bonds, forming chains along [100]. The chains are linked by C—H⋯π interactions, forming slabs parallel to (001).

Crystal structure of 2-methyl­amino-3-nitro-4-p-tolyl­pyrano[3,2-c]chromen-5(4H)-one

In the racemic title compound, C20H16N2O5, the pyran ring adopts a shallow envelope conformation, with the stereogenic C atom displaced from the other atoms by 0.273 (2) Å. The dihedral angle between the fused-ring system and the pendant p-tolyl group is 87.62 (7)°. The molecular conformation is consolidated by an intramolecular N—H⋯O hydrogen bond, which generates an S(6) ring. In the crystal, molecules are linked by C—H⋯O interactions, resulting in [010] chains.

Crystal structure of 4-(4-meth­oxy­phen­yl)-7,7-dimethyl-2-methyl­amino-3-nitro-7,8-di­hydro-4H-chromen-5(6H)-one

In the title compound, C19H22N2O5, the six-membered carbocyclic ring of the chromene moiety adopts an envelope conformation with the dimethyl-substituted C atom as the flap. The pyran ring has a flat-boat conformation. The methoxyphenyl ring is orthogonal to the mean plane of the chromene moiety, with a dihedral angle of 89.97 (8)°. The amine N atom deviates from the chromene mean plane by 0.1897 (16) Å. The methylamine and the nitro group are involved in an intramolecular N—H⋯O hydrogen bond which generates an S(6) ring motif. They are slightly twisted out of the plane of the chromene moiety with torsion angles of C—N—C—O(pyran) = 2.2 (3)° and O(nitro)—N—C—C = −5.6 (2)°. In the crystal, there are only C—H⋯π interactions present, forming inversion-related dimers.

7,7-Dimethyl-2-methyl­amino-4-(4-methyl­phenyl)-3-nitro-7,8-di­hydro-4H-chromen-5(6H)-one

In the title compound, C19H22N2O4, the six-membered cyclohexenone ring of the chromene unit adopts an envelope conformation, with the dimethyl-substituted C atom as the flap, while the pyran ring has a boat conformation. These two mean planes are inclined to one another by 6.65 (13)°·The benzene ring is normal to the 4H-chromene moiety mean plane, making a dihedral angle of 89.18 (5)°. The methylamine and nitro groups are slightly twisted from the chromene moiety mean plane, with torsion angles C—N—C—O = 1.70 (18) and O—N—C—C = 0.15 (18)°. The molecular structure is characterized by an intramolecular N—H⋯O hydrogen bond, which generates an S(6) ring motif. In the crystal, molecules are linked via pairs of weak C—H⋯O hydrogen bonds, forming inversion dimers. These dimers are connected by further C—H⋯O hydrogen bonds, forming sheets lying parallel to (10-1).

(4S*)-2-Methyl-amino-3-nitro-4-(4-nitro-phen-yl)-5,6,7,8-tetra-hydro-4H-chromen-5-one.

The title compound, C16H15N3O6, is asymmetric with a chiral centre located in the pyran ring and crystallizes as a racemate. The six-membered carbocyclic ring adopts an envelope conformation with the central CH2 C atom as the flap. The amine N atom deviates from the mean plane of the pyran ring by 0.1365 (15) Å. The nitrophenyl ring is almost orthogonal to the pyran ring and the mean plane of the six-membered carbocyclic ring, the dihedral angle between their mean planes being 88.30 (7) and 87.61 (8)°, respectively. The molecular structure is stabilized by an intramolecular N—H⋯O hydrogen bond, which generates an S(6) ring motif. In the crystal, molecules are linked via C—H⋯O hydrogen bonds, forming infinite bands lying parallel to (-110) and composed of alternate R 2 2(24) and R 2 4(12) graph-set ring motifs. The crystal structure is further stabilized by C—H⋯π interactions, forming a three-dimensional structure.