*3.2. Phenolic Compounds*

Phenolic compounds are biosynthesized by plants through shikimate, phenylpropanoid, and flavonoid pathways, and have an aromatic ring bearing one or more hydroxyl groups. These compounds have been reported for their antioxidant, antiproliferative, and cytotoxic properties [78]. Many phenolic compounds have been identified elsewhere from the same medicinal plants that are traditionally used to manage cancer in Ethiopia. For instance, (−)-epigallocathechin (**25**) isolated from *Maytenus senegalensis* has showed potent cytotoxic activity against mouse lymphoma cell line (L5178Y) [79]. Likewise, a series phenanthrenes (5-(1-methoxyethyl)-1-methyl-phenanthren-2,7-diol (**26**); effususol A; effusol; dehydroeffusol; dehydroeffusal; 2,7-dihydroxy-1,8-dimethyl-5-vinyl-9,10-dihydrophenanthrene and juncusol; dehydrojuncusol and 1-methylpyrene-2,7-diol) from *Juncus e*ff*uses*inhibited the proliferation of five human cancer cell lines (Table 3). Among these, 5-(1-methoxyethyl)-1-methyl-phenanthren-2,7-diol (**26**) (Figure 3) was tested against MCF-7 cancer cell line and showed better cytotoxic activity [80] than all isolated compounds from *J. e*ff*uses*. Another group of phenanthrenoids (effususol A, **27**) has also demonstrated potent cytotoxicity against HT-22 cell by inducing caspase-3-mediated apoptosis [81]. Plumbagin (**28**), a naphthoquinone isolated from *Plumbago zeylanica* also induced apoptosis in human non-small cell lung (IC50 = 6.1–10.3 μM) [82] and human pancreatic (IC50 = 2.1 μM) [83] cancer cell lines. On the other hand, knipholone (**29**) isolated from *Kniphofia foliosa* Hochst collected from Ethiopia, induced necrotic death in mouse melanoma (B16), mouse macrophage tumor (RAW 264.7), human acute monocytic (THP-1), and promonocytic leukaemic (U937) cell lines with IC50 values that range from 0.5 ± 0.05 to 3.3 ± 0.39 μM [15].

**Figure 3.** Structures of anticancer phenolic compounds reported from plants available in Ethiopia.


**3.**Phenoliccompoundsisolatedfrommedicinalplantsthataretraditionallyusedtotreatcancerin

tumor, THP-1 = human acute monocytic leukaemic, U937 = promonocytic leukaemic;, IC50 = Concentration that inhibited cell proliferation by 50%. \* Plant materialfrom Ethiopia.

 collected

#### *3.3. Alkaloids*

Vinblastine (**30**) and vincristine (**31**) (Figure 4) are one of the most effective bis-indole vinca alkaloids as anticancer drugs, isolated from the leaves of *Catharanthus roseus* [84]. This is one of the most precious anticancer plants indigenous to Madagascar. Previously, approximately 30 bis-indole alkaloids and over 60 monomeric indole alkaloids have been isolated from the aerial parts and roots of *C. roseus* [85,86]. Wang et al. [87] isolated three new cytotoxic dimeric indole alkaloids (**32**–**34**) along with other five known compounds from the whole plant of *C. roseus* collected from China (Table 4). Among the isolated compounds, leurosine (**36**) showed the most potent cytotoxic activity with IC50 value of 0.73 ± 0.06 μM. Furthermore, the isolated three new compounds (**32**–**34**) also showed potent cytotoxicity against triple-negative breast cancer (MDA-MB-231) cell line with IC50 values ranging from 0.97 ± 0.07 μM to 7.93 ± 0.42 μM. Another alkaloid, cathachunine (**40**), also showed a promising cytotoxic activity against HL-60 by inducing an intrinsic apoptotic pathway [88]. On the other hand, the monoterpenoid indole alkaloids vindoline and catharanthine, isolated from Malaysian *V. roseus*, showed weak cytotoxic activity against HCT 116 [89]. Furthermore, colchicine (**41**), isolated from the seeds of *Gloriosa superba*, demonstrated moderate activity against six human cancer cell lines (A549, MCF-7, MDA-MB231, PANC-1, HCT116, and SiHa) [90].

**Figure 4.** Structures of anticancer alkaloids reported from plants present in Ethiopia.


Cell lines: MDA MB 231 = Triple-negative breast cancer, SW480 = Human colorectal, HCT116 = Human colorectal carcinoma, HL60 = Human promyelocytic leukemia, MCF-7 = breastadenocarcinoma,SMMC-7721=Humanhepatocarcinoma,A-549=Humanlungadenocarcinoma,MGC-803=Humangastriccancer.IC50=Concentrationthatinhibited

proliferation by 50%.

 cell

#### *3.4. Steroids and Lignans*

Steroids andlignans, in addition to other phytochemicals, are common secondarymetabolites reported from Ethiopian plants. Evidence and epidemiological studies suggest that phytosterols and lignans are protective against a wide range of diseases and possess anticancer activity [93]. Withanolides are cytotoxic steroidal lactones, reported from various plants of the family Solanaceae [94], of which withaferine-A (**44**) and 5β,6β,14α,15α-diepoxy-4β,27-dihydroxy-1-oxowitha-2,24-dienolide (**45**) (Figure 5), isolated from *Withania somnifera*, demonstrated anticancer activity against human lung cancer cell line (NCI-H460) with IC50 values of 0.45 ± 0.00 and 8.3 ± 0.21 μg/mL, respectively [94]. Several buffadinolides, cardiac glycosides with steroidal nucleus, including berscillogenin, 3-epiberscillogenin, and bersenogenin [95]; hellebrigenin 3-acetate (**48**); and hellebrigenin 3,5-diacetate (**49**) [96] isolated from *Bersama abyssinica* collected from Ethiopia, demonstrated cytotoxic activities. β-Sitosterol-3-*O*-glucoside, a phytosterol from *Prunus Africana*, exhibited poor anticancer activity against three cell lines (Table 5).

Lignans and isoflavonoids are the major classes of phytoestrogens [97] which showed potential anticancer activity against various cells. Three lignans, namely, (−)-carinol (**50**), (−)-carissanol (**51**), and (−)-nortrachelogenin, isolated from *Carissa spinarum*,were found to be cytotoxic against A549, MCF-7, and WI-38 cell lines. Among these, (−)-carinol (i.e., a compound with butanediol structure) showed more potent cytotoxic activity against these three cell lines with IC50 value of 1 μg/mL, as compared to (−)-carissanol and (−)-nortrachelogenin [98]. Secoisolariciresinol (**52**) and matairesino (**53**), two lignans isolated from *Linum usitatissimum*, exhibited cytotoxicity against MCF-7 cells with IC50 values of 10 and 1 μM, respectively [99].


adenocarcinoma,

collected from Ethiopia.

 WI-38 = Normal human embryonic, IC50 =

Concentration

 that inhibited cell proliferation

 by 50%. ED50 = Effective dose for 50% of the population \* Plant material

**Figure 5.** Structures of anticancer steroids and lignans reported from plants available in Ethiopia.
