Chemical Diversity and Bioactivities of Monoterpene Indole Alkaloids (MIAs) from Six Apocynaceae Genera

Abstract

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead.

Keywords: Apocynaceae; alkaloids; anti-inflammatory; antimicrobial; cytotoxicity; monoterpene.

Figure 1

Biogenetic numbering rule as adopted from LeMen and Tylor.

Figure 2

Examples of well-known biologically active terpene indole alkaloids.

Figure 3

The types of the structures identified monoterpenoid alkaloids from the six genera.

Figure 4

Common monoterpenoid indole alkaloidal skeletons of the six genera.

Figure 5

Compounds 1–22.

Figure 6

Compounds 23–30.

Figure 7

Compounds 31–38.

Figure 8

Compounds 39–51.

Figure 9

Compounds 52–60.

Figure 10

Compounds 61–70.

Figure 11

Compounds 71–90.

Figure 12

Compounds 91–97.

Figure 13

Compounds 98–109.

Figure 14

Compounds 110–114.

Figure 15

Compounds 115–135.

Figure 16

Compounds 136–145.

Figure 17

Compounds 146–157.

Figure 18

Compounds 158–170.

Figure 19

Compounds 171–197.

Figure 20

Compounds 198–227.

Figure 21

Compounds 228–253.

Figure 22

Compounds 254–268.

Figure 23

Compounds 269–283.

Figure 24

Compounds 284–303.

Figure 25

Compounds 304–318.

Figure 26

Compounds 319–332.

Figure 27

Compounds 333–353.

Figure 28

Compounds 354–369.

Figure 29

Compounds 370–384.

Figure 30

Compounds 385–394.

Figure 31

Compounds 395–406.

Figure 32

Compounds 407–417.

Figure 33

Compounds 418–444.

Scheme 1

Biosynthesis of corynanthe, aspidosperma and iboga indoles.

Scheme 2

Biosynthesis of ajmaline indole alkaloids. (SB) Sarpagan bridge enzyme; polyneuridine aldehyde reductase (PNAE), vinorine synthase (VS), vinorine hydroxylase (VH), vomilenine reductase (VR), dihydrovomilenine reductase (DHVR) 17-O-acetyl-ajmalanesterase (AAE), norajmaline-N-methyltransferase (NMT).

Figure 34

Number of compounds isolated from the six genera.

Figure 35

Percentage of reported compounds from the species.

Figure 36

Number of compounds identified from different organs.

Figure 37

Number of compounds versus biological activities.