Synthesis, Partial Characterization, and In Vitro Anticancer Activity of Indanocine Analogues Bearing Indanone-Aldehyde Rings Putatively Targeting Tubulin

Undergraduate #24
Discipline: Chemistry and Chemical Sciences
Subcategory: Cancer Research

Diarra Dia - Florida Memorial University
Co-Author(s): Rose Mary Stiffin, Kenneth Doxsee, James Hutchison, Mohammed Nayel, Cesar Ramirez, and Alexandro Lima, Florida International University Duane Miller, Xiangming Kong, Aissata Dia, Josymar Travieso, Lelani Bellieni, and Charlissa Whyms, Florida Memorial University

---

In search of potential therapeutics for cancer, we described herein the synthesis, partial characterization, and in vitro anticancer activity of a series of indanocine – like analogues. The compounds were synthesized using Green Chemistry practices, using solid state synthesis, to decrease exposure of chemist to harmful solvents or catalysts. The synthetic route involved a hallmanr in organic chemistry synthesis, the well-characterized aldol condensation, in which various indanones (both 1 and 2) were coupled with various aromatic aldehydes, using stoichiometric amounts of NaOH as the solid phase catalyst. The anticancer effects were evaluated on a panel of 60 cell lines, according to the National Cancer Institute (NCI) screening protocol. There were approximately a dozen tested compounds among over seventy synthesized compounds that displayed moderate to good (50 – 90% growth inhibition) anticancer activity in one-dose (10 M). The most active compound of the series was (2Z) – 2 – [(2, 4 – dimethoxy) methylidene – 3H – 4 – bromo] – Inden – 1 – one, which showed mean growth percent of 68.49% in one-dose assay. Although this mean indicates the compound could also induce cell growth, it was moderately effective against disparate cell types; for example, it displayed a 15% growth inhibition against the metastatic colon cancer cell line, HCT – 116 and ~ 8% growth inhibition against the metastatic melanoma cell line MDA – MB – 435. It is of interest to note that this compound induced the growth of several renal cancer cell lines. It is unclear as of yet what the target is within the cells; however, the compound bears a striking resemblance to indanocine, a compound that was purported to be a tubulin inhibitor, binding similar to colchicine. Spectral data to confirm the structures of the compounds (GC-MS, 1H – NMR, and 13C – NMR) are forthcoming. Thus far, melting point and TLC suggest all tested compounds are with 95 % purity.

Funder Acknowledgement(s): Rose Mary Stiffin Florida Memorial University

Faculty Advisor: Rose Mary Stiffin, rstiffin@fmuniv.edu

Role: I made the compounds and found their melting point and percent yield.