Table 1.

The bioactivities and sources of BCDO indole alkaloids.

Compound	Source	Bioactivity
Diketopiperazines
	P. brevicompactum2,7,9,30,103,153–163 P. viridicatum10,158,164–167 P. ochraceum11 P. duclauxii168 Penicillium sp.169	Insecticidal activity129,130
	Chemical synthesis26,31
	P. brevicompactum 2,7,9,30,159,166 P. viridicatum 10
	Chemical synthesis22,23,26,31
	P. brevicompactum 7,9,103,160,166	Cytotoxic activity (IC50, 15.6 μM against HCT116 cell line)103
	P. brevicompactum 7,9	Insecticidal activity129
	Chemical synthesis7,159
	P. brevicompactum 2,103
	P. brevicompactum 2,103
	P. brevicompactum 2
	P. brevicompactum 2
	P. brevicompactum 2
	Aspergillus sp.170 Annulohypoxylon cf. stygium171 A. protuberus34 A. versicolor63	Cytotoxic activity (IC50, 27 and 29 μM against HeLa and L1210 cell lines, respectively)34 Inhibition of RANKL-induced osteoclastogenic differentiation133
	A. amoenus 133,172
	A. sulphureus and Isaria felina co-culture132 Fusarium sambucinum134 A. ochraceus131,173 Aspergillus sp.131,174 A. cf. stygium171 A. protuberus34 A. versicolor63	Anticancer activity (~64% inhibition ratio of the colony formation of 22Rv1 prostate cancer cells at 100 μM)132 Anti-inflammatory activity (36.8% and 40.6% inhibition ratios of cytokines IL-1β and TNF-α at the concentration of 20 μM, respectively)131 Cytotoxic activity (IC50, 52 and 36 μM against HeLa and L1210 cell lines, respectively)34 Inhibition of RANKL-induced osteoclastogenic differentiation133
	A. taichungensis 64 A. amoenus 36,172
	A. amoenus 172
	A. sulphureus and I. felina co-culture132 Aspergillus sp.35,170,174 A. ochraceus135 A. ostianus135 A. versicolor135
	A. taichungensis 64
	Aspergillus sp.35 A. ochraceus135	Antitumor (IC50, 244, 87, 219, and 279 nM against SMMC-7721, HCT-8, MCF-7, and HUVEC cell lines, respectively; IC50, 0.66–2.70 μM against various liver cancer cell lines)135
	Photoinduced product175
	Aspergillus sp.35,136	Antifungal activity (MIC, 25 μg/mL against R. solani)136 Anti-inflammatory activity (IC50, 46.2 μM against P. acnes-induced THP-1 cells)136
	A. amoenus 172
	Aspergillus sp.35 A. ochraceus135	Cytotoxic activity (IC50, 21 μg/mL against HeLa cell line)35
	A. amoenus172 Aspergillus sp.136
	A. protuberus 62
	Aspergillus sp.37,176
	A. amoenus 172
	Aspergillus sp.37
	Aspergillus sp.39,136,174 A. ostianus135	Anti-inflammatory activity (IC50, 34.3 μM against P. acnes-induced THP-1 cells)136
	A. amoenus 172
	Aspergillus sp 136
	A. ochraceus 135
	A. sulphureus and I. felina co-culture 132
	Chemical synthesis61
	Chemical synthesis61
	Chemical synthesis61	Inhibition of RANKL-induced osteoclastogenic differentiation (IC50, 1.7 μM against murine RAW264 cells)133
	Chemical synthesis61	Inhibition of RANKL-induced osteoclastogenic differentiation (IC50, 4.4 μM against murine RAW264 cells)133
	A. protuberus 61
	A. protuberus 62
	A. protuberus 62
	A. protuberus 62
	A. protuberus 62
	A. protuberus 62
	A. protuberus 62
	A. protuberus 62
	A. protuberus 62
	Aspergillus sp.39
	A. taichungensis 64
	A. amoenus 172
	A. taichungensis 64
	A. ochraceus 135
	Photoinduced product175
	A. ochraceus 135
	A. ochraceus 135
	A. ochraceus135 Aspergillus sp.136
	A. taichungensis64 A. amoenus36 Aspergillus sp.137 A. ochraceus138	Inhibition of RANKL-induced osteoclastogenic differentiation133 Antibacterial activity (MIC, 14.5 μM against S. epidermidis)137 Mitochondrial respiratory inhibitor (IC50, 34.6 μM against NADH oxidase)138
	A. ochraceus43,131,135,177 Aspergillus sp.174,176 A. tennesseensis178 A. versicolor66,135 A. cf. stygium171 A. protuberus34	Cytotoxic activity (IC50, 1.0–13.1 μM against various human tumor cell lines)43 Anti-inflammatory activity (46.5% and 32.6% inhibition ratios of cytokines IL-1β and TNF-α at the concentration of 20 μM, respectively)131
	A. amoenus 60
	A. taichungensis64,115 Aspergillus sp.62 A. amoenus60	Inhibition of RANKL-induced osteoclastogenic differentiation133
	A. taichungensis 175
	A. ochraceus 43,179 A. westerdijkiae 180	Cytotoxic activity (IC50, 0.06–0.46 μM against various human tumor cell lines; GI50, 135, 346, 91, and 289 nM against LNCap, βT-549, T-47D, and MALME-3M cell lines, respectively)43,181 Antitumor activity (IC50, 0.091, 0.194, 0.403, and 0.268 μM against SMMC-7721, HCT-8, MCF-7, and HUVEC cell lines; IC50, 0.42–3.19 μM against various liver cancer cell lines) 135
	Chemical synthesis182
	Aspergillus sp.37 A. versicolor135
	A. taichungensis64 A. amoenus36 Aspergillus sp.37,62 A. versicolor62,63,135
	A. taichungensis 64
	A. taichungensis 64
	A. taichungensis 64
	A. taichungensis 64
	A. ochraceus 131 A. taichungensis 64	Anti-inflammatory activity (38.9% and 34.5% inhibition ratios of cytokines IL-1β and TNF-α at the concentration of 20 μM, respectively)131
	A. versicolor 66
	A. taichungensis 64 A. cf. stygium 171
	A. taichungensis 64
	A. taichungensis 64
	A. versicolor 65 F. sambucinum 134 A. ochraceus 65,139	Antimicrobial activity (MIC, 4–32 μg/mL against multiple bacteria and fungi; MIC of 0.8 μM against P. aeruginosa)134,139
	Aspergillus sp.174	Anti-biofilm formation activity (IC50, 1.4 μM against Candida albicans)114
	Aspergillus sp.174
	Aspergillus sp.170	Antiproliferative activity (IC50, 0.519, 1.855, 0.62, and 0.78 μM against HT1080, PC3, Jurkat, and A2780S cell lines, respectively)170
	Aspergillus sp.170
	Aspergillus sp.170	Antiproliferative activity (IC50, 1.135, 1.805, 1.79 and 1.127 μM against HT1080, PC3, Jurkat, and A2780S cell lines, respectively)170
	F. sambucinum134 Aspergillus sp.136,174 A. sclerotiorum183 A. ochraceus131,173,177 A. protuberus34 A. sulphureus and I. felina co-culture132	Insecticidal activity (83.2% mortality rate under diet at 500 ppm against Helicoverpa armigera; 46% mortality rate under diet at 200 ppm against Helicoverpa zea)134,183 Antimicrobial activity (MIC, 4–16 μg/mL against multiple bacteria and fungi; MIC of 25 μg/mL against R. solani)134,136 Anti-inflammatory activity (IC50, 41.6 μM against P. acnes-induced THP-1 cells)136 Caseinolytic protease P (ClpP) activator (EC50, 39.6, 87.5, and 2.6 μM for decapeptide (DFAP), FITC-casein, and Hill slope, respectively) 184 Anticancer activity (~65% inhibition ratio of the colony formation of 22Rv1 prostate cancer cells at 100 μM)132
	A. amoenus 55
	A. westerdijkiae 185
	A. sulphureus and I. felina co-culture 132
	A. sulphureus and I. felina co-culture 132
	A. westerdijkiae 185,186
	F. sambucinum 134	Insecticidal activity (70.2% mortality rate under diet at 500 ppm against H. armigera)134 Antimicrobial activity (MIC, 8–32 μg/mL against multiple bacteria and fungi)134
	A. sclerotiorum 187	Cytotoxic activity (IC50, 1.7, 1.6, 1.8, and 1.5 μM against HeLa, A549, HepG2, and SMMC-7721 cell lines, respectively)187
	A. sclerotiorum 187	Cytotoxic activity (IC50 >10 μM against HeLa, A549, HepG2, and SMMC-7721 cell lines)187
	A. sclerotiorum 187	Cytotoxic activity (IC50 >10 μM against HeLa, A549, HepG2, and SMMC-7721 cell lines)187
	A. sclerotiorum 187	Cytotoxic activity (IC50, 7.9, 7.8, 8.1, and 6.7 μM against HeLa, A549, HepG2, and SMMC-7721 cell lines, respectively)187
	A. sclerotiorum 187	Cytotoxic activity (IC50 >10 μM against HeLa, A549, HepG2, and SMMC-7721 cell lines)187
	A. sclerotiorum 187	Cytotoxic activity (IC50 >10 μM against HeLa, A549, HepG2, and SMMC-7721 cell lines)187
	A. amoenus 188
	F. sambucinum 134	Antimicrobial activity (MIC, 1–32 μg/mL against multiple bacteria and fungi)134
	A. ochraceus135,189,190 Aspergillus sp.174,191 A. westerdijkiae180	Antitumor activity (IC50, 0.059, 0.209, 2.443, and 1.225 μM against SMMC-7721, HCT-8, MCF-7, and HUVEC cell lines, respectively; IC50, 0.63–3.39 μM against various liver cancer cell lines; IC50, 1100, 643, 116, 112 and 78 nM against NB4, HL-60, MV4-11, OCI-AML3, and Molm-13 acute myeloid leukemia (AML) cell lines, respectively; GI50 (growth-inhibitory potencies), 0.33 and 0.42 μM against T-47D and LNCap cell lines, respectively; IC90, 1.1 μg/mL against HeLa cell line; GI50, 0.24, 0.62, 0.20, and 0.41 μM against LNCap, βT-549, T-47D, and MALME-3M cell lines, respectively)135,181,189,190,192 Antibacterial activity (MIC, 12.5, 12.5, and 25 μg/mL against Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, respectively)190
	A. taichungensis 64,175
	Chemical synthesis182
	A. ochraceus 115,193
	A. ochraceus 115,193
	Aspergillus sp.136	Antimicrobial activity (MIC, 8–100 μg/mL against multiple bacteria and fungi) 136 Anti-inflammatory activity (IC50, 30.5 μM against P. acnes-induced THP-1 cells)136
	Aspergillus sp.136
	Aspergillus sp.136
	Aspergillus sp.136	Antifungal activity (MIC, 25 μg/mL against R. solani)136 Anti-inflammatory activity (IC50, 30.5 μM against P. acnes-induced THP-1 cells)136
	A. versicolor 194
	A. versicolor 194
	A. versicolor 194
	A. versicolor 194
	A. versicolor 194
	Paecilomyces variotii 194,195	Cytotoxic activity (IC50, 55.9 μM against NCI-H460 cell line)195
	A. tennesseensis 178	Antiproliferative activity (IC50, 83.4 μM against H460 cell)178
	A. tennesseensis 178	Antiproliferative activity (IC50, 95.5 μM against H460 cell)178
	A. tennesseensis 178
	Aspergillus sp. TE-65L196	Anti-inflammatory activity196
	A. taichungensis 299197	Cytotoxic activity (IC50, 19.2, 23.4, 48.5, and 1.7 μM against A549, HeLa, HepG2, and AGS cell lines, respectively)197
Monoketopiperazines
	P. purpurogenum 198 Malbranchea graminicola 69 M. aurantiaca 142	Calmodulin inhibitory activity (IC50, 35.73 μM)142
	P. purpurogenum 198 M. aurantiaca 142
	M. circinate 143 M. aurantiaca 67,68,142,144 M. graminicola 69	Calmodulin inhibitory activity (IC50, 3.65 μM67,141; IC50, 19.33 μM140) Vasorelaxant activity (EC50, 2.7 μM)144 α-Glucosidase (αGHY) inhibitory activity (IC50, 71.3 and 458.7 μM for yeast and rat, respectively)143 Protein Tyrosine Phosphatase 1B (PTP-1B) inhibitory activity (IC50, 14.5 μM)143 Inhibition of radicle growth of Amaranthus hypochondriacus (IC50, 0.37 μM)67
	M. aurantiaca 68,142,144 M. graminicola 69	Calmodulin inhibitory activity (IC50, 183.28 μM)142 Vasorelaxant activity (EC50, 33.3 μM)144
	M. graminicola 69 M. aurantiaca 142,144	Calmodulin inhibitory activity (IC50, 41.56 μM)142 Vasorelaxant activity (EC50, 25.5 μM)144
	M. graminicola 69
	M. graminicola 69
	Enzymatic product93
	Enzymatic product93
	Enzymatic product199
	M. graminicola 69,80
	Enzymatic product80
	Enzymatic product80
	Enzymatic product80
	Enzymatic product80
	P. herquei 200 P. fellutanum 76 A. japonicus A. aculeatinus 79
	Aspergillus sp.81 P. janthinellum78 Penicillium spp.72 P. fellutanum76 A. japonicus76 Penicillium sp.73 P. cluniae77 P. charlesii74	Anthelmintic activity (100% reduction in faecal egg count with dose at 2.0 mg/kg; MIC50 of 31.2 μg/ml in vitro; 98% effective against T. colubriformis infection at an oral dose of 1.56 mg/kg)72,73,146,201 Insecticidal activity (LD50, 2.5 μg/ml against Caenorhabditis elegans; LD50 of 0.32 μg/nymph against O. fasciatus)74,77
	P. charlesii 74 P. cluniae 77	Insecticidal Activity (LD50, 100 μg/ml against C. elegans; LD50, 16.54 μg/nymph against O. fasciatus)74,77
	P. charlesii 74	Insecticidal Activity (LD50, 40 μg/ml against C. elegans)74
	P. charlesii 74	Insecticidal Activity (LD50, 160 μg/ml against C. elegans)74
	Aspergillus sp.81 A. aculeatinus79 A. aculeatus202 P. janthinellum78 P. charlesii74 P. cluniae77	Anthelmintic activity (88, 96, and 99% reductions in faecal egg counts with dose at a dose of 0.5, 1.0, and 2.0 mg/kg against adult T. colubriformis infection, respectively)81 Cytotoxic activity (IC50, 1.9 μM against Bel-7402 cell line)79 Insecticidal activity (LD50, 6 μg/ml against C. elegans; LD50 0.089 μg/nymph against O. fasciatus)74,77
	Penicillium sp.73 P. charlesii74	Insecticidal Activity (LD50, 65 μg/ml against C. elegans)74 Anthelmintic activity (MIC50 >500 μg/ml in vitro)73
	Penicillium sp.73 P. charlesii74	Insecticidal activity (LD50, 20 μg/ml against C. elegans)74 Anthelmintic activity (MIC50 >500 μg/ml in vitro)73
	P. cluniae 77
	P. cluniae 77
	P. janthinellum 78
	A. aculeatinus79 P. simplicissimum ΔphqK80
	P. janthinellum 78
	P. simplicissimum ΔphqK80
	A. aculeatinus79 Penicillium spp.72 Enzymatic product80
	Aspergillus sp.81 A. aculeatinus79 P. janthinellum78 Enzymatic product80
	Penicillium spp. 72 P. cluniae77	Anthelmintic activity (94% reduction in faecal egg count with dose at 2.0 mg/kg)72 Insecticidal activity (LD50, 7.01 μg/nymph against O. fasciatus)77
	Penicillium spp.72 P. cluniae77	Insecticidal activity (LD50, 0.91 μg/nymph against O. fasciatus)77
	P. fellutanum76 Penicillium spp.72,88
	Aspergillus sp.73,81	Anthelmintic activity (MIC50, 15.6 μg/ml in vitro)73
	A. aculeatinus 79	Cytotoxic activity (IC50, 3.3 μM against Bel-7402 cell line)79
	P. herquei 200
	P. herquei 200	Anti-HCV activity (IC50, 5.1 μM)200
	Aspergillus sp.81 A. japonicus203,204	Paralytic activity (against silkworms at a dose of 10 μg/g of diet and 3 μg/g of body weight with injection method)203,204
	Aspergillus sp.81	Anthelmintic Activity (in vitro)81
	A. japonicus 204	Paralytic activity (against silkworms at a dose of 10 μg/g of diet and 3 μg/g of body weight with injection method)204
	A. japonicus 204	Paralytic activity (against silkworms at a dose of 10 μg/g of diet and 3 μg/g of body weight with injection method)204
	P. citrinum 205
	Penicillium sp.206	Protein tyrosine phosphatase 1B (PTP-1B) inhibitory activity (IC50, 27.6 μM)206
	P. purpurogenum 198
	P. purpurogenum 198
	P. oxalicum 207	Brine shrimp (A. salina) lethality (LD50, 5.6 μM)207
	P. oxalicum 208	Cytotoxic activity (IC50, 28.12 μM against HL-60 cell line)208
	P. paneum 209,210 P. roqueforti 211–213 A. carneus 214	Cytotoxic activity210
	P. paneum 209,210 P. roqueforti 211–213	Cytotoxic activity210
	P. paneum 210 P. roqueforti 211–213	Cytotoxic activity210
	P. chrysogenum 215 P. citrinum 216	Neurocyte protection activity (improving cells viability by 59.6% at the concentration of 1 × 10−4 mM)215 Antifungal activity (reduced 61% of P. digitatum radial growth at 400 μg/mL)216
	Penicillium sp.217,218 P. herquei200
	Penicillium sp.217
	Penicillium sp.217,218 P. herquei200	Anti-acetylcholinesterase activity (IC50, 58.0 μM)217
	Penicillium sp.218
	Penicillium sp.218
	Penicillium sp.218
	Penicillium sp.218
	A. duricaulis 219
	A. duricaulis 219
	A. duricaulis 219	Inhibitory effect on Aβ aggregation (IC50, 269.5 μM)219
	A. duricaulis 219
	A. duricaulis 219	Inhibitory effect on Aβ aggregation (IC50, 244.3 μM)219
	A. duricaulis 219
	A. duricaulis 219	Protecting cells against beta-amyloid (Aβ) aggregate-induced toxicity (EC50, 149.6 μM), and inhibiting Aβ aggregation (IC50, 186.6 μM)219
	P. citrinum 4,97
	P. citrinum 97
	P. citrinum 4
	P. citrinum 4
	P. citrinum 97

IC₅₀: half maximal inhibitory concentration. EC₅₀: half maximal effective concentration. LD₅₀: half of the lethal dose. MIC: minimum inhibitory concentration.