Indole alkaloids from Ervatamia orientalis. I. Isolation of alkaloids and structural identification of two dimers

Abstract

Ethanol extracts of Ervatamia orientalis have yielded the following known alkaloids: ibogaine, iboxygaine, voacristine, vobasine, dregamine, tabernaemontanine, apparicine, voacamine and 16- demethoxycarbonylvoacamine. In addition, two new dimeric alkaloids of the voacamine group and the novel 2-acylindoles ervatamine, 20- epiervatamine and 19-dehydroervatamine have been isolated from the extracts. The two new dimeric compounds have been identified by physical and chemical methods as 16-demethoxycarbonyldihydrovoacamine and 16-demethoxycarbonyl-20?-epi-dihydrovoacamine.

Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review

“…Ortusa., 5 Tabernaemontana australis 6 , and Tabernaemontana orientalis. 7 Although known for many centuries for tribes in West Africa, research of ibogaine started in late 19th century. The first description of T. iboga is published in 1985 from specimens of the plant brought to France from Gabon.…”

Evaluation of DNA Binding and Topoisomerase I Inhibitory Activities of 16’‐Decarbomethoxydihydrovoacamine from Tabernaemontana corymbosa

“…Lastly, the selectivity of the bisindole 1 was evaluated using MTT cytotoxicity assay by treating the human normal colon fibroblast CCD18-Co with 1 for 72 h. As oppose to the potent cytotoxicity observed in our previous studies, [3] 1 was relatively less toxic towards CCD18-Co with an IC 50 of 3.91 � 0.14 μM (cisplatin IC 50 2.47 � 0.18 μM). With reference to the IC 50 of bisindole 1 against human colorectal adenocarcinoma HT-29 (0.92 μM), [3] the calculated selectivity index (SI) of 1 was 3.15 and is classified as selective (SI > 2). [19] The high selectivity of the bisindole 1 was in line with the ADMET predictions which are suggesting that 1 is non-toxic (Table 1).…”

“…LRo5 violation [b] 2 2 Veber's rule violation [c] 0 1 Ligand efficiency (LE) metrics [d] [a] %ABS = 109À (0.345 × TPSA) [15] [b] Violate the rules when HBDH � 5, MW � 500.00, Log P � 5.00, MLog P � 4.15, and M_NO � 10 [13] [c] Violate the rules when RB > 10 and TPSA > 140.00 Å 2 [14] [d] Proposed acceptable values as follows: LE ∼ 0.3 kcal per mole per non-hydrogen atom, LLE > ∼ 5 and À 10 < LELP < 10 [17] Lastly, the selectivity of the bisindole 1 was evaluated using MTT cytotoxicity assay by treating the human normal colon fibroblast CCD18-Co with 1 for 72 h. As oppose to the potent cytotoxicity observed in our previous studies, [3] 1 was relatively less toxic towards CCD18-Co with an IC 50 of 3.91 � 0.14 μM (cisplatin IC 50 2.47 � 0.18 μM). With reference to the IC 50 of bisindole 1 against human colorectal adenocarcinoma HT-29 (0.92 μM), [3] the calculated selectivity index (SI) of 1 was 3.15 and is classified as selective (SI > 2). [19] The high selectivity of the bisindole 1 was in line with the ADMET predictions which are suggesting that 1 is non-toxic (Table 1).…”

“…We previously reported the isolation of new cytotoxic iboga‐vobasine bisindoles (vobatensines A–F) from the stem bark extract of T. corymbosa collected from Taiping, Malaysia [2] . In addition to these compounds, the known bisindole 16’‐decarbomethoxydihydrovoacamine ( 1 , Figure 1) [3] was also isolated and was shown to exhibit strong cytotoxicity in a wide array of human cancer cells upon 72 h of treatment, predominantly against colorectal adenocarcinoma HT‐29 (IC 50 0.92 μM) and carcinoma HCT 116 (IC 50 2.9 μM) [3] . However, the anti‐proliferative mechanism and selectivity of the bisindole 1 have not been previously investigated and its relatively higher isolation yield provided an opportunity to initiate such studies.…”

ChemInform Abstract: Naturally Occurring Dimers from Chemical Perspective

“…Catharanthine (145a) first cleaves to 145c under acidic conditions, which can isomerize to 145d and 145e; 145e can be seen as a cation, coupled with the aromatic ring of vindoline (145b) to lead to the key intermediate 145f, which is further converted to 145 after some modifications. There are several other bisindole alkaloids, formed via a similar pathway, such as vincristine (146), leurosine (147), and leurosidine (148) from Catharanthus [88], tabernaelegantine A (149), tabernaelegantine B (150), conodurine (151), and conoduramine (152) [89], as well as (19'R)-hydroxyconodurine (153), (19'R)-hydroxyconoduramine (154), and tabernamine (155) [90] from Tabernaemontana plants, 16-(demethoxycarbonyl)-19,20-dihydro-20-epivoacamine (156) from E. orientalis [91], 16-(demethoxycarbonyl)voacamine (157) from Peschiera fuchsiaefolia [92], ervadivaricatine B (158) [93] from E. officinalis, and 19,20-dihydrotabernamine (159) [94] from T. caffeoides.…”