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The head and neck squamous cell carcinoma (HNSCC) constitute about 90% of all head and neck cancers. HNSCC falls in the top 10 cancers in men globally. Epoxyazadiradione (EPA) and Azadiradione (AZA) are the limonoids derived from the medicinal plant Azadirachta indica (popularly known as Neem). Whether or not the limonoids exhibit activities against HNSCC and the associated mechanism remains elusive. Herein, we demonstrate that EPA exhibits stronger activity in HNSCC in comparison to AZA. The limonoids obeyed the Lipinski's rule of 5. EPA exhibited activities in a variety of HNSCC lines like suppression of the proliferation and the induction of apoptosis. The limonoid suppressed the level of proteins associated with anti-apoptosis (survivin, Bcl-2, Bcl-xL), proliferation (cyclin D1), and invasion (MMP-9). Further, the expression of proapoptotic Bax and caspase-9 cleavage was induced by the limonoid. Exposure of EPA induced reactive oxygen species (ROS) generation in the FaDu cells. N-acetyl-L-cysteine (ROS scavenger) abrogated the down-regulation of tumorigenic proteins caused by EPA exposure. EPA induced NOX-5 while suppressing the expression of programmed death-ligand 1 (PD-L1). Further, hydrogen peroxide induced NF-κB-p65 nuclear translocation and EPA inhibited the translocation. Finally, EPA modulated the expression of lncRNAs in HNSCC lines. Overall, these results have shown that EPA exhibit activities against HNSCC by targeting multiple cancer related signalling molecules. Currently, we are evaluating the efficacy of this molecule in mice models.

Diels-Alder reaction of the cage compound 2 with itself, leading to the highly caged compound 3 , as well as with cyclopentadiene, leading to compounds 4 and 5 , is described.

Photochemical synthesis of the novel compounds 3-bromotetracyclo [5.3.1.02,6.04,8] undec-10(12)-ene-9,11-dione, 1-(bromomethyl)pentacyclo [5.4.0.02,6.03,10.05,9]undeca-8,11-dione and 1-bromo-9-(bromomethyl)pentacyclo [5.4.0.02,6.03,10.05,9]undeca-8,11-dione is described.

In pursuit of Platonic hydrocarbon dodecahedrane1, a retrosynthetic theme indicated in scheme 1, was formulated. The precursor tetraquinanedione synthon5 was first designed through a photo-thermal olefin metathesis approach. The tetraquinanedione 5 was further elaborated toexo, exo-tetraquinane diester15 through carbonyl homologation, oxidation, esterification sequence, scheme 5. Bis-cyclopentannulation ofexo,exo-diester15 by Greene methodology delivered a functionalised C20-hexaquinane44, havingexo-annulated cyclopentane rings. Cyclopentane inversion was achieved by a set of reactions involving enone generation, double bond isomerisation and hydrogenation to give spheroidal (C2v)-C20-hexaquinanedione-diester47, the penultimate precursor of dodecahedrane 1. Several interesting transformations and rearrangements of polyquinanes are also described.