Shrivallabh P. Kamat

A convenient one-pot synthesis of 4-methyl-3-phenyl-, 3-aryl- and 3-aryl-4-phenylcoumarins

Thermal condensation of 2′-hydroxyacetophenones 1a–e with phenylacetic acid 2a in refluxing diphenyl ether gives 4-methyl-3-phenylcoumarins 3a–e. Similarly, reaction of 2-hydroxybenzaldehydes 1f–m and 2-hydroxybenzo-phenones 1n–p with phenylacetic acids 2a–d gives the corresponding 3-arylcoumarins 3f–m and 3-aryl-4-phenylcoumarins 3n–p respectively. Formation of esters 4 and 5 and benzofuran 6 is also observed.

Inulavosin and its benzo-derivatives, melanogenesis inhibitors, target the copper loading mechanism to the active site of tyrosinase

Tyrosinase, a melanosomal membrane protein containing copper, is a key enzyme for melanin synthesis in melanocytes. Inulavosin inhibits melanogenesis by enhancing a degradation of tyrosinase in lysosomes. However, the mechanism by which inulavosin redirects tyrosinase to lysosomes is yet unknown. The analyses of structure–activity relationship of inulavosin and its benzo‐derivatives reveal that the hydroxyl and the methyl groups play a critical role in their inhibitory activity. Intriguingly, the docking studies to tyrosinase suggest that the compounds showing inhibitory activity bind through hydrophobic interactions to the cavity of tyrosinase below which the copper‐binding sites are located. This cavity is proposed to be required for the association with a chaperon that assists in copper loading to tyrosinase in Streptomyces antibioticus. Inulavosin and its benzo‐derivatives may compete with the copper chaperon and result in a lysosomal mistargeting of apo‐tyrosinase that has a conformational defect.

Synthesis of 7,8-methylenedioxy-4'-methoxyisoflavone from Indigofera linnaei and two new related flavonoids

The synthesis of naturally occurring 7,8-methylenedioxy-4′-methoxyisoflavone and 7,8-methylenedioxy-4′-methoxy-flavone from 2′-hydroxy-3′,4′-methylenedioxy-4-methoxychalcone via the intermediacy of 7,8-methylenedioxy-4′-methoxyflavanone using thallium(III) acetate and catalytic amount of perchloric acid is reported. The products flavanone and the flavone are new flavonoids characterised by spectral analysis.

Long Chain Alkyl Esters of Hydroxycinnamic Acids as Promising Anticancer Agents: Selective Induction of Apoptosis in Cancer Cells

Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16, and C18 alkyl esters of p-coumaric, ferulic, sinapic, and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC50 values of 0.123 ± 0.012, 0.301 ± 0.069 and 1.0 ± 0.1 μM, respectively. Compounds 1c, 1d, and 4c significantly increased apoptotic cells in sub-G1 phase and activated the caspase-3 enzyme in MOLT-4 cells. Compound 1c was 15.4 and 23.6 times more potent than doxorubicin and cisplatin, respectively, against the drug resistant MES-SA-DX5 uterine sarcoma cells. These p-coumarate esters were several times less effective against NIH/3T3 fibroblast cells. Docking studies showed that 1c may cause cytotoxicity by interaction with carbonic anhydrase IX. In conclusion, long chain alkyl esters of p-coumaric acid are promising scaffolds for selective apoptosis induction in cancer cells.

Single crystal X-ray analysis of isomeric 2-(2,4,4-trimethyl-3,4-dihydro-2h-benzo[h]× chromen-2-yl)-1-naphthyl acetate and 3-(2,4,4-trimethyl-3,4-dihydro-2H-benzo[g]× chromen-2-yl)-2-naphthyl acetate

Single crystal X-ray structure characterization of isomeric 2-(2,4,4-trimethyl-3,4-dihydro-2H-benzo[h]chromen-2-yl)-1-naphthyl acetate (1) and 3-(2,4,4-trimethyl-3,4-dihydro-2H-benzo[g]chromen-2-yl)-2-naphthyl acetate (2) is described. Compound 1 crystallizes in the centrosymmetric monoclinic space group P21/c with all atoms situated in general positions. Isomeric compound 2 crystallizes in the centrosymmetric triclinic space group P-1 and its structure consists of two crystallographically independent molecules with all atoms located in general positions. In addition to intramolecular C-H…O bonding, 2 is involved in two intermolecular C-H…O interactions resulting in a one-dimensional H-bonded network.

Synthesis of 5'-bromo-2'-hydroxy-4,4',6'-trimethoxychalcone from Garcinia nervosa and of its isomer 3'-bromo-2'-hydroxy-4,4',6'- trimethoxychalcone

The unambiguous syntheses of the naturally occurring 5′-bromo-2′-hydroxy-4,4′,6′-trimethoxychalcone 1, a constituent of Garcinia nervosa, and its positional isomer 3′-bromo-2′-hydroxy-4,4′,6′-trimethoxychalcone 6 are described.

Sodium metaperiodate oxidation of isocarvacrol

Sodium metaperiodate oxidation of isocarvacrol 8, a monoterpene phenol has been found to give hydrothymoquinone 13, a natural product and a ring cleavage product 7-oxo-5-isopropyloct-3-en-2,5-olide 14.