Antifungal activity against Fusarium oxysporum of quinolizidines isolated from three controlled-growth Genisteae plants: structure–activity relationship implications

Abstract

The Genisteae tribe belongs to the Fabaceae family. The wide occurrence of secondary metabolites, explicitly highlighting the quinolizidine alkaloids (QAs), characterizes this tribe. In the present study, twenty QAs (1–20), including lupanine (1–7), sparteine (8–10), lupanine (11), cytisine and tetrahydrocytisine (12–17), and matrine (18–20)-type QAs were extracted and isolated from leaves of three species (i.e., Lupinus polyphyllus ('rusell' hybrid), Lupinus mutabilis, and Genista monspessulana) belonging to the Genisteae tribe. These plant sources were propagated under greenhouse conditions. The isolated compounds were elucidated by analyzing their spectroscopical data (MS, NMR). The antifungal effect on the mycelial growth of Fusarium oxysporum (Fox) of each isolated QA was then evaluated through the amended medium assay. The best antifungal activity was found to be for compounds 8 (IC50 = 16.5 µM), 9 (IC50 = 7.2 µM), 12 (IC50 = 11.3 µM), and 18 (IC50 = 12.3 µM). The inhibitory data suggest that some QAs could efficiently inhibit Fox mycelium growth depending on particular structural requirements deduced from structure–activity relationship scrutinies. The identified quinolizidine-related moieties can be involved in lead structures to develop further antifungal bioactives against Fox.

Quinolizidine-Type Alkaloids: Chemodiversity, Occurrence, and Bioactivity

“…Alkaloid 2 significantly inhibited migration and invasion of human gastric cancer cells by decreasing phospho-cofilin (Ser3) and phospho-LIMK1 (Thr508) without changing the total expression of cofilin and LIMK1 . In addition, alkaloid 7 showed acaricidal and aphicidal effects on Tetranychus cinnabarinus and Aphis citricola , respectively, and antifungal activity against Botryosphaeria dothidea and Fusarium oxysporum …”

“…216 In addition, alkaloid 7 showed acaricidal and aphicidal effects on Tetranychus cinnabarinus and Aphis citricola, 217 respectively, and antifungal activity against Botryosphaeria dothidea 218 and Fusarium oxysporum. 219 It has been reported that the consumption of seeds from Lupinus plants containing alkaloid 62 has led to intoxication events in humans due to the acute anticholinergic toxicity of some lupanine-type QAs. The most common symptoms are blurred vision, dry mouth, easy flushing, and confusion.…”

“…Recent studies have evaluated the antifungal activity of compounds 2, 7, 15,56,59,62,63,92,94,110,132,133,139,160,161,174, and 239 against the phytopathogen Fusarium oxysporum, involving IC 50 values between 10 and 400 μM. 219 On the other hand, some studies were performed on the effect of quinolizidines 351−354 against Candida albicans ATCC 14503, C. albicans UCD-FR1, C. glabrata, and C. krusei, with MIC values between 30 and 100 μg/mL. 191 Other studies have evaluated the antibacterial activity of compounds 65, 133, 138, and 251 against Enterococcus faecalis, with MIC values between 20 and 200 μg/mL.…”

“…132 – 136 showed remarkable activity against HPIV-3 with a selectivity index (SI) of 58, calculated as the ratio of CC 50 /IC 50 . Compounds 148 – 155 isolated from seeds of Thermopsis lanceolata had moderate insecticidal activity against Aphis fabae (LC 50 = 43.15 and 46.47 mg/L, respectively), and compound 132 showed antifungal activity against Fusarium oxysporum . On the other hand, compounds 150 – 151 isolated from the rhizomes of the Chinese plant known as “ Shan-Dou-Gen ” ( Sophora tonkinensis ) were evaluated against the cancer lines T24 (human bladder cancer cell line), SPC-A2 (human lung adenocarcinoma), and A549 (human lung adenocarcinoma).…”

“…The antimicrobial effect of QAs has been evaluated against several microorganisms such as bacteria and fungi. Recent studies have evaluated the antifungal activity of compounds 2 , 7 , 15 , 56 , 59 , 62 , 63 , 92 , 94 , 110 , 132 , 133 , 139 , 160 , 161 , 174 , and 239 against the phytopathogen Fusarium oxysporum , involving IC 50 values between 10 and 400 μM . On the other hand, some studies were performed on the effect of quinolizidines 351 – 354 against Candida albicans ATCC 14503, C .…”