2.B.92.  The Indole-2-Carboxamide Derivative (I2CD) Family

Salunke et al. 2019 explored an indole-2-carboxamide derivative 117-ONB (see figure below) in which the amide group was protected by an ortho-nitrobenzyl group. This ortho-nitrobenzyl group was photo-cleavable, and irradiation with 345 nm light released the active carrier. The transport activity of 117 and 117-ONB after different irradiation times was explored in EYPC liposomes using the HPTS fluorescence assay. The results confirmed the activity of 117 and the lack of response in the case of the nonirradiated sample of 117-ONB. Irradiation of samples containing 117-ONB induced a transport efficiency close to that observed for 117, suggesting the efficient release of the active form from the photocaged procarrier. Although the irradiation needed to achieve this process was not ideal for biological studies, these processes were also studied in living cells. The cytotoxic effects of both 117-ONB and 117 in MCF 7 cells were limited. This observation was explained in terms of the inactivity of 117-ONB as a carrier and the limited solubility of 117, which precipitated in the media under these conditions. Nevertheless, irradiation of the cells treated with 117-ONB with 365 nm light for 5 minutes induced pronounced cell death at 24 h. Control experiments indicated that irradiation or treatment with the photo-released by-product (o-nitrosobenzaldehyde) of the cell cultures resulted in negligible cytotoxicity. Thus, this strategy allowed the deliverance of the procarrier which upon irradiation resulted in the active carrier capable of inducing the cytotoxic effect (Davis et al. 2020).

Photocaged pro-carrier 117-ONB is converted to carrier 117 by light.




Davis, J.T., P.A. Gale, and R. Quesada. (2020). Advances in anion transport and supramolecular medicinal chemistry. Chem Soc Rev. [Epub: Ahead of Print]

Salunke, S.B., J.A. Malla, and P. Talukdar. (2019). Phototriggered Release of a Transmembrane Chloride Carrier from an o-Nitrobenzyl-Linked Procarrier. Angew Chem Int Ed Engl 58: 5354-5358.