Mahidansha M. Shaikh

Design and synthesis of novel carbazolo–thiazoles as potential anti-mycobacterial agents using a molecular hybridization approach

Various substituted carbazolo–thiazoles (compounds 6a–6o) were synthesized in good yields using a molecular hybridization approach. The synthesized compounds were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at the National Institute of Allergy and Infectious Diseases (Bethesda, MD, USA). Among the tested series, compound 6c (minimum inhibitory concentration 21 μM) showed the most promising anti-mycobacterial activity. Brief structure–activity relationship studies showed that the electron-donating groups (OCH3 and OH), particularly on the phenyl ring of the thiazole motif, had a positive correlation with the anti-mycobacterial activity. In addition, they displayed low cytotoxicity against a mammalian Vero cell line using the MTT assay, thereby having a high therapeutic index. This study shows the importance of molecular hybridization and the scope for the development of carbazole–thiazole compounds as potential anti-mycobacterial agents.

Anti-inflammatory activities of selected synthetic homoisoflavanones

Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were previously isolated from Caesalpinia pulcherrima, were synthesised to determine their anti-inflammatory activity and cytotoxicity. A range of four different homoisoflavanones (compounds 4a–4d) were synthesised from the corresponding substituted phenols.1H- and 13C-NMR data together with high-resolution mass spectroscopy data were employed to elucidate the structures. Anti-inflammatory activity was determined in mice with acute croton oil-induced auricular dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose-dependent manner after 3 and 6 h of treatment. Compounds 4b–4d also inhibited oedema, although a clear dose-response relationship was not observed. Compounds 4a–4c were found to be less cytotoxic than compound 4d. Compound 4b was the least cytotoxic. Compounds 4a–4d exhibited anti-inflammatory activity and varying levels of cytotoxicity.

(E)-3-(4-Cyclo­hexyl-3-fluoro­benzyl­idene)chroman-4-one

The title compound, C22H21FO2, exhibits substitutional disorder of the F atom and a H atom in the asymmetric unit with different occupancies, the refined F:H ratio being 0.80 (2):0.20 (2). The dihedral angle between the fluorinated benzene ring and the benzene ring of the chromanone system is 37.30°. There are two relatively high residual electron-density peaks associated with the disorder.

3-Bromo­chroman-4-one

The heterocyclic ring of the title compound, C9H7BrO2, obtained by bromination of 4-chromanone with copper bromide, adopts a half-chair conformation. The supramolecular structure is governed by a weak C—H⋯O hydrogen bond. There is also π–π stacking between symmetry-related benzene rings; the centroid–centroid distance is 3.9464 (18), the perpendicular distance between the rings is 3.4703 (11) and the offset is 1.879 Å.

3-(3-Nitro-benz-yl)-4H-chromen-4-one.

In the title compound, C16H11NO4, the dihedral angle between the 10-membered coplanar chromone ring system and the benzene ring is 77.83 (3)°. In the crystal, weak C—H⋯O hydrogen bonds link the molecules into a three-dimensional network.

2,4-Dibromo-1,3-dimeth-oxy-5-methyl-benzene.

The title compound, C9H10Br2O2, crystallizes with two molecules in the asymmetric unit. The two molecules are essentially planar with slight differences in the (Br)C—C—O—C(H3) torsion angles [−176.7 (2) and −172.8 (2)° in one molecule and 174.8 (2) and 179.9 (2)° in the other]. The crystal structure consists of sheets of molecules linked through Br⋯Br [3.3547 (4), 3.3703 (4) and 3.5379 (4) Å] interactions, which are in turn connected through π–π interactions with centroid–centroid distances of 3.5902 (14) and 3.5956 (14) Å.

3-(3,4-Dichloro-benzyl-idene)chroman-4-one.

The distinctive feature of the structure of the title compound, C16H10Cl2O2, is the formation of a zigzag chain along [100] via Cl⋯Cl interactions [3.591 (1) and 3.631 (1) Å]. The chromanone moiety is fused with the benzene ring and adopts a half-chair conformation. The dihedral angle between the benzene ring of the chromanone moiety and the dichlorobenzene plane is 56.14 (8)°.

3-(3-Meth­oxy­benzyl­idene)chroman-4-one

In the title compound, C17H14O3, the dihedral angle between the methoxybenzene unit and the benzene ring of the chromanone system is 64.12 (3)°. The crystal structure is stabilized by weak C—H⋯O interactions.

3-Benzyl-5,7-dimeth­oxy­chroman-4-ol

In the crystal structure of the title compound, C18H20O4, O—H⋯O hydrogen bonds connect the molecules in parallel layers along the b axis.