Table 1.

Nobiletin (NOB) and its derivatives reduce the IC₅₀ of paclitaxel (PTX) for multidrug resistant HCT8/T cancer cells.

Compd.	R1	R2	R3	R4	X	Cytotoxicity IC50 (μmol/L)a	Cytotoxicity of combination IC50 (μmol/L)b	Reversal foldc
PTX	–	–	–	–	–	5.89 ± 0.24	5.89 ± 0.24	1
7a	OMe	OMe	OMe		O	>100	0.14 ± 0.01	43
7b (NOB)	OMe	OMe	OMe		O	44.67 ± 3.83	0.030 ± 0.002	185
7c	OMe	OMe	OMe		O	38.46 ± 3.30	0.080 ± 0.004	81
13	H	OMe	OMe		O	74.99 ± 4.04	0.090 ± 0.005	66
16	Br	OMe	OMe		O	>100	0.15 ± 0.01	40
18	NH2	OMe	OMe		O	66.83 ± 3.99	0.29 ± 0.05	21
23a	OMe	H	H		O	66.83 ± 2.73	0.29 ± 0.01	21
23b	OMe	H	H		O	69.98 ± 6.78	0.44 ± 0.04	14
23c	OMe	H	H		O	39.36 ± 4.41	0.36 ± 0.02	17
23d	OMe	OMe	H		O	66.83 ± 2.73	0.13 ± 0.01	47
28	OMe	OMe	OMe		NH	>100	0.23 ± 0.02	27
29a	OMe	OMe	OMe		NMe	26.61 ± 2.63	0.11 ± 0.01	55
29b	OMe	OMe	OMe			21.13 ± 1.77	0.15 ± 0.01	40
29c	OMe	OMe	OMe			59.57 ± 3.62	0.24 ± 0.01	26
29d	OMe	OMe	OMe			>100	0.070 ± 0.008	87

‒Not applicable.

^aIntrinsic cytotoxicity of target compounds or PTX alone to HCT8/T cells.

^bValues of IC₅₀ for cytotoxicity of combination (P-gp inhibitor 10 μmol/L + PTX) were as mean ± SD of at least three independent experiments.

^cThe reversal fold was calculated as a ratio of IC₅₀ (PTX) to IC₅₀ (P-gp inhibitor 10 μmol/L + PTX).