Compounds identified from the marine Sea Urchin (Diadema savignyi) as Potential Anti-Cancer Drug Candidate against Human Colorectal Cancer: A Bioinformatics Approaches

Abstract

Abstract The occurrence of colorectal cancer is estimated to increase by 1.9 million people by 2020, making it the second most common chronic disease. Yet, no specific drug candidates for treating this cancer have been developed or made accessible. However, the nuclear transport receptor importin-11 transports β-catenin to the nucleus and regulates the proliferation of colorectal cancer cells. The inhibition of importin-11 can block the β-catenin nuclear import and the growth of APC-mutant colorectal cancer cells. As a result, this research aimed to discover natural anti-cancer drugs that can block the function of importin-11, inhibiting the progression of colorectal cancer. The structure of 19 compounds isolated from sea urchins was initially determined using gas chromatography-mass spectrometry (GC-MS). Consequently, a molecule docking, absorption, distribution, metabolism, and excretion (ADME) approach and a molecular dynamics (MD) simulation approach were used to screen the compounds. Four molecules were initially identified with PubChem: CID 11955, CID 605775, CID 608814, and CID 6432458. Pharmacokinetics and toxicity for all compounds have been evaluated. To confirm the stability of their binding to the target protein, each compound was assessed using MD simulation methods. An in silico method revealed the top four compounds that could have pharmacological interest with a higher affinity for the target protein. Altogether, we describe here that compounds from sea urchins show interesting anti-cancer activity against importin-11, which could potentially be used to develop an anti-CRC drug. Therefore, further experimental validation is recommended to ensure a comprehensive assessment of their mechanism of action.