Table 6.

SARs Associated with Compound 3^a

position/scaffold	SAR
	Methylene group is essential for inhibiting DDX5, down-regulating survivin expression and dispensing of topoisomerase 1 inhibition.78
	R9 position on ring I is tolerant of modifications with the substituted benzene (R-Ph) ring decreasing cytotoxicity (e.g., 59 and 60).164,168
	R7 on ring II is tolerant of modifications with different rings; Five-membered heterocyclic rings are generally better than a six-member pyridine or benzene ring.82
	The lactone ring V may be unstable under acidic or basic conditions that may undermine 3’s activity and stability.170
	The free hydroxy group on ring V is critical for cytotoxicity;167 Protection by hydrophilic groups via ester bond such as that in 61 and compounds 62–65 reduces cytotoxicity.167,169

^aThe highlighted elements are the points of discussion.