In the bioassays of the compounds tested, compounds b3 and b4 exhibited a high degree of activity towards Gram positive
B. subtilis; Compounds a14 and a18 dispalyed a high degree of activity towards R. solanacearum.
In conclusion, 45 calycanthaceous alkaloid derivatives with the tetrahydropyrroloindole core structure were synthesized
by modification at the 8-N position and evaluated for their antibacterial activity against five strains of bacteria (B. cereus,
B. subtilis, S. aureus, E. coil, R. solanacearum, and P. aeruginosa). The bioassays indicated that among the synthesized
compounds, compounds b3 and b4 exhibited a high degree of activity towards Gram positive B. subtilis. Compounds a14 and
a18 displayed a high degree of activity towards R. solanacearum. These results will pave the way for further design, structural
modification, and development of calycanthaceous alkaloids as antibacterial agents.
EXPERIMENTAL
General. All reagents and solvents were of reagent grade or purified according to standard methods before use.
Analytical thin-layer chromatography (TLC) was performed with silica gel plates using silica gel 60 GF (Qingdao Haiyang
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Chemical Co., Ltd.). Melting points were measured on an electrothermal digital apparatus made in Beijing and were uncorrected.
1
13
The H NMR (500 MHz) and C NMR (125 MHz) were obtained on a Bruker AM-500 FT-NMR spectrometer with CDCl as
3
the solvent and TMS as the internal standard. MS were recorded under ESI conditions using a Thermo LCQ Fleet instrument.
Optical rotation was measured by a Rudolph Autopol II polarimeter. The title compounds were synthesized under nitrogen
atmosphere.
Synthesis. The general synthetic methods for compounds a1–a24 and b1–b21 are depicted in Scheme 1 [21, 22].
Biological Assay. The antibacterial activity of calycanthaceous alkaloid analogues was measured according to a
previously reported method [22].
Filter PaperAssay. The antibacterial activities of compounds against five strains of bacteria (B. cereus, B. subtilis,
S. aureus, E. coil, R. solanacearum, and P. aeruginosa) were evaluated by the filter paper assay. The standard bacterial strains
were obtained from the College of Plant Protection, Northwest A & F University. Ampicillin (Sigma, Shanghai, China) was
used as a positive control. Beef extract peptone agar was used as the assay medium. The medium was mixed with a suspension
containing the bacterial pathogen. Next, the mixture was poured onto 9 cm Petri dishes. The tested compounds were dissolved
in acetone at the concentration of 2000 ppm. The filter papers (6 mm in diameter) were impregnated with 5 ꢀL/disc of each
compound, then completely dried and placed on the inoculated agar. The inoculated plates were incubated at 37ꢁC for 24 h.
Antibacterial activity was evaluated by measuring the zone of inhibition against the test organism. Experiments were run in
triplicate.
ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of China (31360079, 21372185, and 21502073),
the Natural Key Research and Development Program of China (No. 2017YFD0200506), the Natural Science Foundation of
Jiangsu Province (Grants No. BK 20150465), and the Marine Equipment and Technology Institute of Jiangsu University of
Scince and Technology.
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