1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

Table 1

Relative structure-function relationships of calcium antagonists (DHPs, verapamil, and diltiazem) and vitamin E. Effect on oxidative modification of isolated ex vivo human low-density lipoprotein using two various oxidation systems (copper (II) ions induced and monocyte induced). Compiled according to data presented by Rojstaczer and Triggle [119].

Compound	Systems of LDL oxidation
	Copper (II) ions induced system (comparison of three methods)			Monocyte induced cell oxidation system
	Methods
	Reduction of TBARS level of LDL (relative efficacy)	Degradation of oxidized [^125I] LDL by J774 macrophages	Relative electrophoretic mobility of LDL on agarose gel	TBARS content of LDL; (in %%)
	Relative efficacy (activity rank order (ARO); ARO = I for the most effective); effective inhibitor concentration [IC], in M
Amlodipine	+ +; (ARO = IV)	+ +; (ARO = II–V)	25 M; 50 M	25 M; (ARO = III–V)
Felodipine	+ + + + +; (ARO = I)	+ + +; (ARO = I); 25 M, %	50 M	25 M, %; (ARO = II)
Nifedipine	+ + +; (ARO = III)	+ +; (ARO = II–V)	10 M; 50 M	25 M, %; (ARO = I)
2-Chloro analog of nifedipine	+ + + +; (ARO = II)	—	—	—
4-Nitro analog of nifedipine	—	+ +; (ARO = II–V)	—	25 M; (ARO = III–V)
Nitrendipine	+ +; (ARO = IV)	—	No effect	—
Verapamil	+ +; (ARO = IV)	+ +; (ARO = II–V)	—	25 M; (ARO = III–V)
Diltiazem	+; (ARO = V)	—	No effect	—
-Tocopherol; (vitamin E)	+ + + + + +; (ARO = I)	—	1 M; 5 M; 10 M; 50 M	—