*4.12. Renieramycin M*

Renieramycin M (RM) (22-Boc-Gly-RM), produced by *Xestospongia sp.,* is a semisynthetic amino ester derivative of the bistetrahydroisoquinoline alkaloid. Studies suggested RM-mediated inhibition of anchorage-independent development and sensitization of detachment-induced cell death in human lung cancer cells [92]. A semi-synthetic derivative of RM with a hydroquinone amino ester extension was synthesized to retain cytotoxicity with increase cancer selectivity [93]. It hinders the phosphorylation of FAK and Akt molecules, which upregulate TIMP2 and TIMP3 and downregulate MMPs expression. The inhibition of the p-FAK/p-Akt signal also marks the downregulation of CDH2 and Rac1-GTP and the upregulation of E-cadherin, where the regulation of cytoskeleton regulatory protein (Rac1-GTP), MMP-associated molecules (TIMP2, TIMP3) [94]. The mechanism of action of RM is demonstrated in Figure 3.

**Figure 3.** Inhibition of the FAK/AKT signaling pathway and subsequently decrease EMT markers, CDH2 MMPs, etc., and increases epithelial marker, E-cadherin, which reduces cell invasion and migration by Renieramycin M and Carnosic Acid [94,95].
