**5. Biological activities**

Isoflavonoids are reported to have a variety of bioprotective effects, including antioxidant, antimutagenic, anticarcinogenic and antiproliferative activities. Isoflavonoids may protect the body from hormone-related cancers, like breast, endometrial (uterine) and prostatic [115–119]. Isoflavonoids have gained a lot of public interest due to the possible correlation between their dietary consumption and health beneficial effects toward osteoporosis and post-menopausal symptoms [120, 121].

Among the isoflavonoids isolated from dothideomycetes fungus CMU-99, Biochanin A (**59**) showed weak cytotoxic activity against lung cancer cells (NCI-H137) and noncancerous Vero cells. Dothideoisoflavanone (**212**) exhibited cytotoxic effect against oral human carcinoma (KB) but was non-toxic against noncancerous Vero cells [9]. Among the isoflavonoids isolated from *Erythrina addisoniae*, Echrenone b10 (**100**) was found to be more than three times as potent as tamoxifen against MCF7/ADR and MDA-MB-231. Erythraddison III (**182**) was twice as potent as tamoxifen [23]. The isoflavanone Ormosinol (191) significantly inhibited adenocarcinomic human alveolar basal epithelial cells (A549) and human hepatic cell line (HepG2) [25]. Neobavaisoflavone (**110**) and Sigmoidin H (**207**) were selectively active *in vitro* against the resistant cancer cells 6/9, 4/9, CCRF-CEM, HCT116 (p53+/+), MDA-MB-231-BCRP and U87MG [40]. Platyisoflavanone A (**32**) showed cytotoxic effect against noncancerous Vero cells [41]. 2″,6″-O-diacetyloninin (**54**) was active against human stomach carcinoma (Hs 740.T, Hs 756 T), breast adenocarcinoma (Hs 578 T, Hs 742.T) and prostate carcinoma (DU 145, LNCaP-FGC) cell lines [70]. Pierreione A (**79**) and Pierreione B (**93**) demonstrated selective toxicity to solid tumor cell lines with minimal cytotoxicity [77]. Isosideroxylin (**117**) was selectively active against the against ER− MDA-MB-231 breast cancer cell line [84]. (3*R*) 5′,8-Di-(γ,γ-dimethylallyl)-2′,5-dihydroxyl-4′,7-dimethoxylisoflavanone (**203**) isolated from *Uraria clarkei* possessed good activity against the tested Hela, K562 and HL60 cell lines [101].

Haginin E (Phenoxodiol) (**254**) inhibits cell proliferation of a wide range of human cancer cell lines including leukemia, breast and prostate carcinomas, and is 5–20 times more potent than genistein [122]. Primary ovarian cancer cells resistant to conventional chemotherapy undergo apoptosis following Haginin E (Phenoxodiol) (**254**) treatment. Haginin E (Phenoxodiol) (**254**) is an efficient inducer of cell death in ovarian cancer cells and sensitizes the cancer cells to Fas-mediated apoptosis [123]. Haginin E (Phenoxodiol) (**254**) also exhibits significant ability to induce cell death in the prostate cancer cell lines LNCaP, DU145 and PC3 that utilize different signaling pathways than those reported in ovarian cancer studies [124]. Haginin E (Phenoxodiol) (**254**) development as an antitumor drug was based to a large extent on its low toxicity in normal tissues, but potent topoisomerase-II inhibitory effects in rapidly dividing tumor cells. This advantage led to its fast-track FDA approval for Phase II/ III clinical trials [125].

Platyisoflavanone A (**32**) showed antibacterial activity against *Mycobacterium tuberculosis* (TB) in the microplate alamar blus assay (MABA) [41]. Isoflavonoids isolated from roots of *Erythrina zeyheri* were tested against methicillin-resistant *Staphylococcus aureus* (MRSA). Anti-MRSA potency of the isoflavan Eryzerin C (**18**) was the highest followed by Eryzerin D (**19**) [44]. 5,7,3′-Trihydroxy-4′-methoxy-6,5′-di(γ, γ-dimethylallyl)-isoflavanone (**173**) isolated from *Erythrina costaricensis* was also active on MRSA [94]. The two isoflavans 3*S* (+) 2′-O-Methylphaseollidinisoflavan (**15**) and 3*R*(-)Erythbidin A (**16**) isolated from *E. caffra* as well as the two isoflavanones 5,7-Dihydroxy-2′-methoxy-3′,4′-methylenedioxyisoflavanone (**31**) and 4′,5-Dihydroxy-2′,3′-dimethoxy-7-(5-hydroxyoxychromen-7yl)-isoflavanone (**155**) isolated from *Uraria picta* were active against *S. aureus* [45, 55]. The isoflavone Neoraudiol (**111**) displayed antimicrobial activity on *Bacillus subtilis, Salmonella typhii* and *Candida albicans* [52]. Lachnoisoflavone A (**91**) from *Crotalaria lachnophora* showed moderate inhibitory activities against *Escherichia coli* and *Klebsiella pneumonia* [76].

**5. Biological activities**

82 Flavonoids - From Biosynthesis to Human Health

**Figure 7.** Isolated isoflavenes from natural sources since 2000 to date.

symptoms [120, 121].

Isoflavonoids are reported to have a variety of bioprotective effects, including antioxidant, antimutagenic, anticarcinogenic and antiproliferative activities. Isoflavonoids may protect the body from hormone-related cancers, like breast, endometrial (uterine) and prostatic [115–119]. Isoflavonoids have gained a lot of public interest due to the possible correlation between their dietary consumption and health beneficial effects toward osteoporosis and post-menopausal

Among the isoflavonoids isolated from dothideomycetes fungus CMU-99, Biochanin A (**59**) showed weak cytotoxic activity against lung cancer cells (NCI-H137) and noncancerous Vero cells. Dothideoisoflavanone (**212**) exhibited cytotoxic effect against oral human carcinoma (KB) but was non-toxic against noncancerous Vero cells [9]. Among the isoflavonoids isolated from *Erythrina addisoniae*, Echrenone b10 (**100**) was found to be more than three times as potent as tamoxifen against MCF7/ADR and MDA-MB-231. Erythraddison III (**182**) was twice as potent as tamoxifen [23]. The isoflavanone Ormosinol (191) significantly inhibited adenocarcinomic human alveolar basal epithelial cells (A549) and human hepatic cell line (HepG2) [25]. Neobavaisoflavone (**110**) and Sigmoidin H (**207**) were selectively active *in vitro* against the resistant cancer cells 6/9, 4/9, CCRF-CEM, HCT116 (p53+/+),

Isoflavanones from the Stem of *Cassia siamea* were evaluated for their anti-tobacco mosaic virus (Anti-TMV) activities [102]. (3*R*) 7,2′,4′-Trihydroxy-3′-methoxy-5-methoxycarbonylisoflavanone (**205**) was the most active among the tested compounds [102]. In addition to anti-TMV, cordifoliflavanes A (**236**) cordifoliflavanes B (**237**) expressed anti-HIV-1 activities [109].

As a part of plant phenolics, isoflavonoids are expected to have antioxidant activities. Ormosinol (**191**) showed significant antioxidant activity against DPPH radicals [25]. The isoflavene Haginin A (**247**) and the isoflavonones dalbergioidin (**153**) showed antioxidant properties in both 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) assays [29]. Seputheisoflavone (**132**) from *Ptycholobium contortum* was active in the ABTS assay [87]. Isoflavones from the *Astragalus mongholicus* were examined for antioxidant potential in DPPH assay. Results indicated that Calycosin (**81**) and Calycosin-7-Oglucopyranoside (**108**) are more active than Formononetin (**58**) [80].

The *in vitro* antiprotozoal activity of isoflavan quinines from *Abrus precatorius* was tested against *Plasmodium falciparum* (K1 strain), *Trypanosoma brucei rhodesiense* (STIB 900 strain), *Trypanosoma cruzi* (Tulahuen strain C2C4 w/LacZ) and *Leishmania donovani* (strain MHOM/ ET/67/L82). Abruquinone D (**239**) and abruquinone K (**241**) were the most active against *T. brucei rhodesiense* [38]. Pumilanol (**29**), an isoflavan from *Tephrosia pumila*, exhibited significant antiprotozoal activities against *T. brucei rhodesiense, T. cruzi* and *L. donovani* [46]. Sophoronol C (**164**) and Sophoronol E (**166**) exhibited moderate anitplasmodial activity against the CQS D10 strain of *P. falciparum* [91].

Daidzein (**64**) and Daidzin (**65**) possess a vasorelaxant action through opening of K+ channels and inhibition of Ca2+ influx in the vascular smooth muscle cells. This cerebral vasodilator activity may be beneficial to patients with obstructive cerebrovascular diseases [126].

Other studies reported on the effects of isoflavonoids on specific enzymes are presented in **Table 7**.


**Table 7.** Effect of isoflavonoids on specific enzyme activities.
