. 2021 Jun 7;26(11):3459. doi: 10.3390/molecules26113459

Table 4.

Bioactivity of bisindole alkaloids (including semisynthetic derivatives) from Alstonia species.

Bisindoles	Bioactivity	References
(+)-Alstomacroline 1	Antimalarial, with IC₅₀ values of 1.12 ± 0.35 and 10.0 ± 0.4 μM against the K1 strain and T9-96 strain of P. falciparum, respectively.	[20]
(+)-Alstomacrophylline 2	Antimalarial, with an IC₅₀ value of 1.10 ± 0.30 μM against the K1 strain of P. falciparum.	[20]
Angustilongines E, F, G, H, J, and K (6–11)	Anticancer, cytotoxic against various human cancer cell lines including KB, vincristine-resistant KB, HCCT 116, PC-3, MDA-MB-231, LNCaP, MCF7, HT-29, and A549 cells with IC₅₀ values ranging from 0.02 to 9.0 μM.	[5]
(−)-Lumusidine A, B, and C (14–16)	Anticancer, moderately cytotoxic in KB/VJ300 cells with IC₅₀ values of 0.16, 0.70, and 1.19 μg/mL (μM), respectively. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(−)-Lumusidine D 17	Anticancer, cytotoxic in KB/VJ300 cells with an IC₅₀ value of 5.03 μg/mL (μM). The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
Lumutinine A, B, C, D, and E (18–22)	Anticancer, moderately cytotoxic in KB/VJ300 cells with IC₅₀ 0.21, 0.10, 4.61, 3.93, and 2.74 μg/mL (μM) values, respectively. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-Macralstonine 24	Anticancer, strongly cytotoxic in KB/VJ300 cells with an IC₅₀ 1.71 μg/mL (μM) value. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-Macralstonine 24	Antimalarial, active against the K1 strain of P. falciparum with an IC₅₀ 8.92 ± 2.95 μM value.	[20]
(−)-Anhydromacralstonine 27	Anticancer, moderately cytotoxic in KB/VJ300 cells with an IC₅₀ value of 0.44 μg/mL (μM). The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-O-Acetyl macralstonine 25	Antimalarial, with IC₅₀ values 0.53 ± 0.09 and 12.4 ± 1.6 (μM) against the K1 strain and T9-96 strain of P. falciparum, respectively.	[20]
(+)-O-Methyl macralstonine 26	Antimalarial, active against the K1 strain of P. falciparum with an IC₅₀ 0.85 ± 0.20 μM value.	[20]
O-Acetyl-E-seco-macralstonine 53	Anticancer, strongly cytotoxic in KB/VJ300 cells with an IC₅₀ value of 0.27 μg/mL (μM). The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(−)-Perhentidine A 36 and (-)-perhentidine B 37	Anticancer, strongly cytotoxic in KB/VJ300 cells with IC₅₀ values of 2.29 and 0.84 μg/mL (μM), respectively. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(−)-O-Acetylperhentidine A 54 and (-)-O-Acetylperhentidine B 55	Anticancer, strongly cytotoxic in KB/VJ300 cells with IC₅₀ 0.36 and 0.28 μg/mL (μM) values, respectively. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(−)-Perhentinine 39 and O-Acetylperhentinine 56	Anticancer, cytotoxic in KB/VJ300 cells with IC₅₀ values of 0.52 and 0.30 μg/mL (μM), respectively. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-Macralstonidine 23	Anticancer, moderately cytotoxic in KB/VJ300 cells with an IC₅₀ value of 0.13 μg/mL (μM). The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-Macrocarpamine 21	Anticancer, strongly cytotoxic in KB/VJ300 cells with an IC₅₀ value of 0.53 μg/mL (μM). The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-Macrocarpamine 21	Strong antimalarial activity against the K1 strain of P. falciparum with an IC₅₀ value of 0.36 ± 0.06 μM. Active against the T9-96 strain of P. falciparum with an IC₅₀ >39 μM value.	[20]
	Strong antiprotozoal activity in vitro against E. histolytica and P. falciparum with ED₅₀ 8.12 (95% C.I.) μM and ED₅₀ 9.36 (95% C.I.) μM values, respectively.	[43]
(+)-Villalstonine 43	Anticancer, cytotoxic in KB/VJ300 cells with an IC₅₀ value of 0.42 μg/mL (μM). The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
	Anticancer, cytotoxic against the HT-29 cell line with an ED₅₀ 8.0 μM value (paclitaxel was used as the positive control).	[39]
	Antimalarial, with IC₅₀ values of 0.27 ± 0.06 and 0.94 ± 0.07 μM against the K1 strain and T9-96 strain of P. falciparum, respectively.	[20]
	Antiamoebic activity against E. histolytica with an ED₅₀ of 2.04 μM.	[43]
Villalstonine N(4)-oxide 44	Antileishmanial activity against promastigotes of L. mexicana with an IC₅₀ value of 80.3 μM (amphotericin B was used as the positive control).	[39]
Villalstonine N(4)-oxide 44	Antimalarial, active against the K1 strain of P. falciparum with an IC₅₀ 10.7 ± 1.9 (μM) value.	[20]
(+)-Villalstonidine B 48 and (+)-villalstonidine F 52	Anticancer, strongly cytotoxic in KB/VJ300 cells with IC₅₀ values of 0.35 and 5.64 μg/mL (μM), respectively. The assay with 0.12 μM added vincristine did not influence KB/VJ300 cell growth.	[18]
(+)-Villalstodinine D 50	Antileishmanial, active against promastigotes of L. mexicana with an IC₅₀ value of 120.4 μM (amphotericin B was used as the positive control).	[39]
(+)-Villalstonidine E 51	Anticancer, cytotoxic against HT-29 cell lines with an ED₅₀ 6.5 μM value (paclitaxel was used as the positive control).	[39]
(+)-Villalstonidine E 51	Antileishmanial against promastigotes of L. mexicana with an IC₅₀ 78 μM value (amphotericin B was used as the positive control).	[39]