Synthesis and in vitro Anticancer Activities of some Selenadiazole Derivatives

Abstract

A novel series of fourteen substituted selenadiazoles has been synthesized and the compounds tested for their in vitro antiproliferative and cytotoxic activities. The tests were carried out against leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54), and breast (MCF-7) cancer cells. In order to assess the selectivity of the compounds under investigation the assays were also carried out on two non-tumoral lines - one mammary (184B5) and one bronchial epithelium (BEAS-2B) cell line. Assay-based antiproliferative activity studies revealed that seven derivatives (2a, 2c, 2e, 2f, 2g, 3a, and 3b) exhibited good activity against MCF-7 cells: for instance, 2c and 2f inhibited cell growth with nanomolar GI₅₀ values. Compound 2f had a better antitumoral profile than vinorelbine and paclitaxel, two drugs that are used as first-line treatments in advanced, recurrent, and/or metastatic cancer. In the other cell lines the compounds showed moderate activity or were inactive - with the exception of 2a, which was also found to have antiproliferative activity. Modulation of the cell cycle and apoptotic effects of active compounds were further evaluated in MCF-7 cells. Of these, 6-bromo[1,2,5]selenadiazolo[3,4-b]pyridine (2a) was the most active, with an apoptogenic effect 3.9 times higher than that of camptothecin, which was used as a positive control. Compound 2a also provoked cell cycle arrest with a significant decrease in the G₀/G₁ phase cell population and an increase in S and G₂/M cells, thus suggesting mitotic arrest prior to metaphase.

Antileishmanial activity of imidothiocarbamates and imidoselenocarbamates

“…Taking into account these considerations, and as part of our ongoing search for biologically active Se-containing compounds (Plano et al 2007;Sanmartín et al 2009;Plano et al 2010), we have analyzed the biological activity of a small in-house compound collection of alkyl imidoselenocarbamates (alkyl isoselenourea) and alkyl imidothiocarbamates (alkylisothiourea) against Leishmania parasites. Our research group has developed these structures based on aromatic and heteroaromatic rings ( Fig.…”

Spectroscopic characterization, photoinduced processes and cytotoxic properties of substitutedN-ethyl selenadiazoloquinolones

“…Consequently, considerable effort has been directed towards the synthesis of stable organoselenium compounds, with potential applications as antioxidants, enzyme modulators, antitumors, antivirals, antimicrobials, antihypertensive agents and cytokine inducers. [2,[7][8][9][10] Nowadays, antimicrobial agents with a quinolone structure represent attractive therapeutic agents due to their unique mechanism of action and bactericidal properties. [11][12][13] Despite long-lasting research efforts which have provided a number of promising drug candidates, quinolones can still offer new analogues of both scientific and clinical interest.…”

New Selenoderivatives as Antitumoral Agents

“…Bearing this fact in mind, and as a continuation of our previous work, we proposed the synthesis 1,2,5-selenadiazolo [3,4-d]pyridines and 1,2,5-benzoselenadiazolo derivatives (Figure 8). The most promising molecule was a pyridine derivative (Plano et al, 2010b). Other explored structures were compounds with selenocyanate and diselenide moieties.…”