9-Arylimino noscapinoids as potent tubulin binding anticancer agent: chemical synthesis and cellular evaluation against breast tumour cells.

A library of 9-arylimino derivatives of noscapine was developed by coupling of Schiff base containing imine groups. Virtual screening using molecular docking with tubulin revealed three molecules, 12-14 that bind with high affinity. An improved predicted free energy of binding (FEB) of -5.390, -6.506 and -6.679 kcal/mol for the molecules 12-14 was found compared to noscapine (-5.135 kcal/mol). Furthermore, molecular dynamics simulation in combination with Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) revealed robust binding free energy of -166.03, -169.75 and -170.63 kcal/mol for the molecules 12, 13 and 14, respectively. These derivatives were strategically synthesized and experimentally validated for their anticancer activity. Tubulin binding assay revealed substantial binding of molecules 12-14 with purified tubulin. Further, their anticancer activity was demonstrated using two cancer cell lines (MCF-7 and MDAMB-231) and a panel of primary breast tumour cells. All these derivatives inhibited cellular proliferation in all the cancer cells that ranged between 30.1 and 5.8 µM, which is 1.7 to 7.52 fold lower than that of noscapine. Further, these novel derivatives arrest cell cycle in the G2/M-phase followed by induction of apoptosis. Thus, 9-arylimino noscapinoids 12-14 have a great potential to be a novel therapeutic agent for breast cancers.

Unusual presentation of follicular carcinoma thyroid with special emphasis on their management.

INTRODUCTION: Follicular carcinoma of thyroid usually behaves in an indolent manner with low metastatic potential. Distant metastases as initial presentation is rare in follicular carcinoma; especially in young patients. PRESENTATION OF CASE: We report the clinical, pathological features and the management of three different cases of follicular carcinoma of the thyroid with unusual presentations at the time of diagnosis. First case presented as thyroid abscess, second case with a large skull swelling in a pre-exiting goiter and the third case with a swelling in the sternum. DISCUSSION: Follicular carcinoma of thyroid is the second category of well-differentiated thyroid cancer that constitutes about 10% of all thyroid malignancies. Blood borne metastasis is common with spread to lung, bone and other solid organs. In less than 10% cases of follicular carcinoma, there is evidence of lymphatic involvement. The patients' presentations above are highly unusual. CONCLUSION: Recognizing these cases has a significant impact on clinical decision-making and prognosis of the patients. Treatment in these patients should be individualized and an alternative therapeutic approach should be considered.