Table 2.

Overview of physicochemical, HSP-inducing properties, and cardioprotective effects of GGA-derivatives in HL-1 cardiomyocyte model and Drosophila

Compound		Physicochemical properties						HL-1 mouse atrial cardiomyocytes						Drosophila melanogaster
		Structural formula	Molecular formula	Molecular weight	LogP	H-bond acceptor	H-bond donor	HSPA1A boosting (protein)		CaT (pretreatment)		CaT (posttreatment)		Contractile function
								Fold induction ± SD	P-value	Protection (yes/no)	P-value	Protection (yes/no)	P-value	Protection (yes/no)	P-value
GGA			C23H38O	330.56	6.54	√		37±15	<0.01	Yes	<0.0001	Yes	<0.0001	Yes	<0.0001
FA			C18H30O	262.43	5.02	√		0.6±0.4
GA			C13H22O	194.32	3.49	√		39±17	<0.01
GGA analog	GGA*-01		C24H40O	344.57	7.2	√		0.52±0.32
	GGA*-02		C19H32O	276.46	5.67	√		1±1.07
	GGA*-03		C23H35F3O	384.52	7.03	√		0.25±0.08
	GGA*-04		C18H27F3O	316.4	5.5	√		52±19	<0.01
	GGA*-05		C13H19F3O	248.28	3.97	√		78±11	<0.01
	GGA*-06		C29H42O	406.64	7.72	√		43±11	<0.01
	GGA*-07		C24H40O	344.57	7.11	√		32±9	<0.01
Geranyl oxims	GGA*-08		C13H23NO	209.33	3.88	√	√	0.57±0.54
And keto-iso-oxalzoles	GGA*-09		C14H25NO	223.35	4.14	√	√	0.57±0.7
	GGA*-10		C23H39NO	345.56	6.93	√		0.5±0.16
	GGA*-11		C24H41NO	359.59	7.19	√		0.48±0.07
Geranyl keto-esters	GGA*-12		C16H26O3	266.38	3.16	√		0.44±0.08
	GGA*-13		C17H28O3	280.4	3.72	√		0.52±0.4
	GGA*-14		C23H32O3	356.5	5.33	√		160±21	<0.0001	No
	GGA*-15		C21H36O3	336.51	5.39	√		0.33±0.08
	GGA*-16		C18H30O3	294.43	4.14	√		0.37±0.2						No
	GGA*-17		C19H32O3	308.46	4.56	√		0.41±0.2
	GGA*-18		C18H30O3	294.43	4.43	√		101±14	<0.001	Yes	<0.0001			No
	GGA*-19		C18H28O5	324.41	2.74	√		0.4±0.2
	GGA*-20		C23H30O3	354.48	5.09	√		15±7	<0.05
	GGA*-21		C20H32O5	352.45	3.34	√		13±5	<0.05
	GGA*-22		C6H10O3	130.14	-0.13	√		0.3±0.2
	GGA*-23		C16H30O3	270.41	4.1	√		17±4
	GGA*-24		C22H30O3	342.47	4.76	√		0.5±0.3
	GGA*-25		C19H22O3	298.38	4.15	√	√	0.4±0.2
	GGA*-26		C21H28O4	344.44	4.48	√	√	31±10	<0.01	Yes	<0.01
	GGA*-27		C16H26O3	266.38	3.07	√		0.3±0.1
Pyrazolones	GGA*-28		C14H22N2O	234.34	3.92	√	√	78±8	<0.01	Yes	<0.0001	No		No
	GGA*-29		C15H24N2O	248.36	4.15	√	√	0.4±0.4
	GGA*-30		C21H28N2O	324.46	5.89	√	√	0.5±0.2
Diketones	GGA*-31		C15H24O2	236.35	1.09	√		155±20	<0.0001	Yes	<0.0001	Yes	<0.05	Yes	<0.05
Geranyl ketones I	GGA*-32		C14H24O	208.34	4.14	√		32±16	<0.01	Yes	<0.05
	GGA*-33		C15H26O	222.37	4.56	√		1±1
	GGA*-34		C16H28O	236.39	4.98	√		15±12	<0.05
	GGA*-35		C17H30O	250.42	5.4	√		14±10	<0.05
	GGA*-36		C15H26O	222.37	4.71	√		0.5±0.08
Geranyl ketones II	GGA*-37		C20H28O	284.44	5.75	√		0.3±0.3
	GGA*-38		C18H32O	264.45	5.81	√		0.5±0.56
	GGA*-39		C15H24O2	220.35	4.21	√		0.4±0.5
	GGA*-40		C8H14O	126.2	1.96	√		0.65±0.3
	GGA*-41		C19H26O	270.41	5.1	√		0.62±0.2
	GGA*-42		C13H22O2	210.31	2.43	√	√	0.42±0.008
	GGA*-43		C13H20O2	208.3	2.29	√		0.9±0.8
	GGA*-44		C15H24O3	252.35	5.75	√		13±3	<0.05
Pyrazoles/isoxazoles	GGA*-45		C15H24N2	232.36	4.3	√	√	15±5	<0.05
	GGA*-46		C16H26N2	246.39	4.53	√		14±8	<0.05
	GGA*-47		C18H27N3	285.43	4.57	√		0.4±0.5
	GGA*-48		C17H28N2O	276.42	4.01	√	√	0.5±0.3
	GGA*-49		C15H23NO	233.35	4.37	√		0.4±0.2
	GGA*-50		C21H27FN2	326.45	6.35	√		0.3±0.2
	GGA*-51		C21H27FN2	326.45	6.35	√		0.6±0.4
	GGA*-52		C22H27N3	333.47	6.23	√		0.4±0.2
Isosters	GGA*-53		C12H21NO	195.3	2.04	√	√	0.6±0.3
	GGA*-54		C13H24N2O	222.34	2.29	√	√	0.4±0.3
	GGA*-55		C17H23FN2O	290.38	3.77	√	√	0.3±0.2
	GGA*-56		C14H23NO3	253.34	1.71	√	√	33±8	<0.01	No
	GGA*-57		C14H21NO2	235.32	1.96	√	√	90±12	<0.001	Yes	<0.0001			No
	GGA*-58		C14H26N2O	238.37	1.86	√	√	95±14	<0.001	Yes	<0.0001	No		Yes	<0.01
	GGA*-59		C11H21NO2S	231.35	1.59	√	√	157±19	<0.0001	Yes	<0.0001	Yes	<0.0001	Yes	<0.0001
	GGA*-60		C11H18F3NO2S	285.33	3.77	√	√	162±21	<0.0001	Yes	<0.0001	Yes	<0.0001	Yes	<0.01
	GGA*-61		C17H25NO2S	307.45	4.26	√	√	15±5	<0.05
	GGA*-62		C15H26O4S	302.43	2.14	√		0.3±0.2
	GGA*-63		C13H23NO3S	273.39	0.69	√	√	0.4±0.3
	GGA*-64		C19H16O4	308.33	2.97	√	√	0.4±0.4
	GGA*-65		C16H28O3	268.39	3.33	√	√	0.6±0.3
	GGA*-66		C13H24O	196.33	3.5	√	√	0.5±0.1
	GGA*-67		C14H25NO	223.45	3.11	√	√	13±3	<0.05
	GGA*-68		C12H20O2	196.29	2.72	√		0.3±0.1
	GGA*-69		C16H27NO2	265.39	3.3	√		0.3±0.4
	GGA*-70		C12H20O3	212.29	1.66	√	√	15±4	<0.05
	GGA*-71		C17H28O4	296.4	2.86	√		17±6	<0.05
Not in a group	GGA*-72		C11H12O4	208.21	1.28	√	√	33±8	<0.01	No
	GGA*-73		C19H30O5	338.44	3.3	√		0.6±0.2
	GGA*-74		C15H25NO3	267.36	3.14	√	√	0.4±0.2
	GGA*-75		C15H26N2O2	266.38	1.38	√	√	45±6	<0.001	No
	GGA*-76		C14H23NO3	253.34	2.42	√	√	0.2±0.1
	GGA*-77		C15H25NO3	267.36	2.36	√	√	0.5±0.1	<0.05
	GGA*-78		C17H23NO2	273.37	3.55	√	√	0.6±0.4
	GGA*-79		C4H5O2	88.11	0.29	√		22±5	<0.05
	GGA*-80		C18H31NO2	293.44	4.13	√		0.7±0.5
	GGA*-81		C22H37NO3	363.53	4.69	√		0.3±0.1