# Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate Didemnum Species

## TL;DR

Scientists isolated new compounds from a Red Sea tunicate, one of which strongly inhibits cancer cell growth and could lead to new anticancer drugs.

## Contribution

The discovery of didemnosides A and B, novel antiproliferative nucleosides with potential for drug development.

## Key findings

- Didemnoside A (compound 1) inhibited MCF-7 cancer cells with an IC50 of 0.597 μM.
- Compounds 1, 2, and 4–7 moderately inhibited SW-1222 and PC-3 cancer cells with IC50 values between 5.25 and 9.36 μM.
- Molecular docking showed stable interactions with cancer-related targets like ESR1, TOP2A, and CDK5.

## Abstract

Marine tunicates are a very attractive and abundant source of secondary metabolites with chemical diversity and biological activity. Fractionation and purification of the organic extract of the Red Sea tunicate Didemnum species resulted in the isolation and identification of three new compounds, didemnosides A and B (1 and 2) and 1,1′,3,3′-bisuracil (3), together with thymidine (4), 2′-deoxyuridine (5), homarine (6), and acetamide (7). Planar structures of the compounds were explained through analyses of their 1D (1H and 13C) and 2D (1H–1H COSY, HSQC, and HMBC) NMR spectra and high-resolution mass spectral determinations. Compound 1 exhibited the highest growth inhibition toward the MCF-7 cancer cell line with IC50 values of 0.597 μM, while other compounds were inactive (≥50 μM) against this cell line. On the other hand, compounds 1, 2, and 4–7 moderately inhibited SW-1222 and PC-3 cells with IC50 values ranging between 5.25 and 9.36 μM. Molecular docking analyses of the top three active compounds on each tested cell line exposed stable interactions into the active pockets of estrogen receptor alpha (ESR1), human topoisomerase II alpha (TOP2A), and cyclin-dependent kinase 5 (CDK5) which are contemplated as essential targets in cancer treatments. Thus, compound 1 represents a scaffold for the development of more effective anticancer drugs.