Discovery of cryptolepine derivatives as novel promising agents against phytopathogenic bacteria

Ying-Hui He, Qing-Ru Chu, Shao-Yong Zhang, Li-Rong Guo, Yue Ma, Bao-Qi Zhang, Zhi-Jun Zhang, Wen-Bin Zhao, Yong-Mei Hu, Chen-Jie Yang, Sha-Sha Du, Tian-Lin Wu, Ying-Qian Liu

PDF(12223 KB)
PDF(12223 KB)
Front. Chem. Sci. Eng. ›› 2023, Vol. 17 ›› Issue (2) : 156-166. DOI: 10.1007/s11705-022-2196-5
RESEARCH ARTICLE

Discovery of cryptolepine derivatives as novel promising agents against phytopathogenic bacteria

Author information +
History +

Abstract

To ensure the production of food crops, a series of cryptolepine derivatives were synthesised, after which their antibacterial activities and mechanism of action against three plant pathogens were investigated. Our bioassay results indicated that most of the target compounds displayed potent inhibitory effects against Xanthomonas oryzae (X. oryzae) and Xanthomonas axonopodis pv. citri (X. axonopodis pv. c.). Remarkably, compound 9 exhibited the best in vitro antibacterial activity against X. oryzae, with a minimum inhibitory concentration (MIC) value of 0.78 μg·mL–1. Compound 2 exhibited the best in vitro antibacterial activity against X. axonopodis pv. c., with an MIC value of 0.39 μg·mL–1. These activities were superior to those of copper quinolate (MIC = 6.25, 25 μg·mL–1) and thiodiazole copper (MIC = 100, 200 μg·mL–1) against X. oryzae and X. axonopodis pv. c. In vivo experiments demonstrated the promising applicability of compound 9 for the control of rice bacterial infections. Furthermore, compound 9 was selected as a candidate to conduct preliminary analyses of the antibacterial mechanisms of cryptolepine derivatives. Scanning electron microscopy and transmission electron microscopy observations, extracellular polysaccharide production, biofilm formation, transcriptomic, quantitative reverse transcription-polymerase chain reaction analyses, and molecular docking assays were performed. Collectively, our findings demonstrated that compound 9 might act via multifarious mechanisms to down-regulate virulence factors and cause cell death.

Graphical abstract

Keywords

cryptolepine derivatives / phytopathogenic bacteria / antibacterial activity / mechanism of action

Cite this article

Download citation ▾
Ying-Hui He, Qing-Ru Chu, Shao-Yong Zhang, Li-Rong Guo, Yue Ma, Bao-Qi Zhang, Zhi-Jun Zhang, Wen-Bin Zhao, Yong-Mei Hu, Chen-Jie Yang, Sha-Sha Du, Tian-Lin Wu, Ying-Qian Liu. Discovery of cryptolepine derivatives as novel promising agents against phytopathogenic bacteria. Front. Chem. Sci. Eng., 2023, 17(2): 156‒166 https://doi.org/10.1007/s11705-022-2196-5

References

[1]
LiP, HuD, XieD, ChenJ, JinL, SongB. Design, synthesis, and evaluation of new sulfone derivatives containing a 1,3,4-oxadiazole moiety as active antibacterial agents. Journal of Agricultural and Food Chemistry, 2018, 66( 12): 3093– 3100
CrossRef Google scholar
[2]
WangP Y, WangM W, ZengD, XiangM, RaoJ R, LiuQ Q, LiuL W, WuZ B, LiZ, SongB A, YangS. Rational optimization and action mechanism of novel imidazole (or imidazolium)-labeled 1,3,4-oxadiazole thioethers as promising antibacterial agents against plant bacterial diseases. Journal of Agricultural and Food Chemistry, 2019, 67( 13): 3535– 3545
CrossRef Google scholar
[3]
ZhangD, ZhouY, ZhaoD, ZhuJ, YangZ, ZhuM. Complete genome sequence and pathogenic genes analysis of Pectobacterium atroseptica JG10-08. Genes & Genomics, 2017, 39( 9): 945– 955
CrossRef Google scholar
[4]
WuS, ShiJ, ChenJ, HuD, ZangL, SongB. Synthesis, antibacterial activity, and mechanisms of novel 6-sulfonyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives. Journal of Agricultural and Food Chemistry, 2021, 69( 16): 4645– 4654
CrossRef Google scholar
[5]
FanX J, KongD, HeS, ChenJ Z, JiangY, MaZ Q, FengJ T, YanH. Phenanthrene derivatives from Asarum heterotropoides showed excellent antibacterial activity against phytopathogenic bacteria. Journal of Agricultural and Food Chemistry, 2021, 69( 48): 14520– 14529
CrossRef Google scholar
[6]
MontenegroI, ValenzuelaM, ZamoranoN, SantanderR, BaezC, MadridA. Activity of Adesmia boronioides resinous exudate against phytopathogenic bacteria. Natural Product Research, 2021, 35( 12): 2072– 2075
CrossRef Google scholar
[7]
LinL B, GaoY Q, HanR, XiaoJ, WangY M, ZhangQ, ZhaiY J, HanW B, LiW L, GaoJ M. Alkylated salicylaldehydes and prenylated indole alkaloids from the endolichenic fungus Aspergillus chevalieri and their bioactivities. Journal of Agricultural and Food Chemistry, 2021, 69( 23): 6524– 6534
CrossRef Google scholar
[8]
LinL B, XiaoJ, ZhangQ, HanR, XuB, YangS X, HanW B, TangJ J, GaoJ M. Eremophilane sesquiterpenoids with antibacterial and anti-inflammatory activities from the endophytic fungus Septoria rudbeckiae. Journal of Agricultural and Food Chemistry, 2021, 69( 40): 11878– 11889
CrossRef Google scholar
[9]
XiangM, ZhouX, LuoT R, WangP Y, LiuL W, LiZ, WuZ B, YangS. Design, synthesis, antibacterial evaluation, and induced apoptotic behaviors of epimeric and chiral 18β-glycyrrhetinic acid ester derivatives with an isopropanolamine bridge against phytopathogens. Journal of Agricultural and Food Chemistry, 2019, 67( 48): 13212– 13220
CrossRef Google scholar
[10]
XiangM, SongY L, JiJ, ZhouX, LiuL W, WangP Y, WuZ B, LiZ, YangS. Synthesis of novel 18β-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases. Pest Management Science, 2020, 76( 9): 2959– 2971
CrossRef Google scholar
[11]
JiangS, SuS, ChenM, PengF, ZhouQ, LiuT, LiuL, XueW. Antibacterial activities of novel dithiocarbamate-containing 4H-chromen-4-one derivatives. Journal of Agricultural and Food Chemistry, 2020, 68( 20): 5641– 5647
CrossRef Google scholar
[12]
JiangS, TangX, ChenM, HeJ, SuS, LiuL, HeM, XueW. Design, synthesis and antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. citri and Ralstonia solanacearum of novel myricetin derivatives containing sulfonamide moiety. Pest Management Science, 2020, 76( 3): 853– 860
CrossRef Google scholar
[13]
ChenY J, LiuH, ZhangS Y, LiH, MaK Y, LiuY Q, YinX D, ZhouR, YanY F, WangR X, HeY H, ChuQ R, TangC. Design, synthesis, and antifungal evaluation of cryptolepine derivatives against phytopathogenic fungi. Journal of Agricultural and Food Chemistry, 2021, 69( 4): 1259– 1271
CrossRef Google scholar
[14]
LavradoJ, CabalG G, PrudencioM, MotaM M, GutJ, RosenthalP J, DiazC, GuedesR C, dos SantosD J, BichenkovaE, DouglasK T, MoreiraR, PauloA. Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies. Journal of Medicinal Chemistry, 2011, 54( 3): 734– 750
CrossRef Google scholar
[15]
FigueirasM, CoelhoL, WichtK J, SantosS A, LavradoJ, GutJ, RosenthalP J, NogueiraF, EganT J, MoreiraR, PauloA. N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors: design, synthesis and antiplasmodial activity. Bioorganic & Medicinal Chemistry, 2015, 23( 7): 1530– 1539
CrossRef Google scholar
[16]
MudududdlaR, MohanakrishnanD, BharateS S, VishwakarmaR A, SahalD, BharateS B. Orally effective aminoalkyl 10H-indolo[3,2-b]quinoline-11-carboxamide kills the malaria parasite by inhibiting host hemoglobin uptake. ChemMedChem, 2018, 13( 23): 2581– 2598
CrossRef Google scholar
[17]
YuanJ M, WeiK, ZhangG H, ChenN Y, WeiX W, PanC X, MoD L, SuG F. Cryptolepine and aromathecin based mimics as potent G-quadruplex-binding, DNA-cleavage and anticancer agents: design, synthesis and DNA targeting-induced apoptosis. European Journal of Medicinal Chemistry, 2019, 169 : 144– 158
CrossRef Google scholar
[18]
QinQ P, WeiZ Z, WangZ F, HuangX L, TanM X, ZouH H, LiangH. Imaging and therapeutic applications of Zn(II)-cryptolepine-curcumin molecular probes in cell apoptosis detection and photodynamic therapy. Chemical Communications (Cambridge), 2020, 56( 28): 3999– 4002
CrossRef Google scholar
[19]
OlajideO A, AjayiA M, WrightC W. Anti-inflammatory properties of cryptolepine. Phytotherapy Research, 2009, 23( 10): 1421– 1425
CrossRef Google scholar
[20]
OlajideO A, BhatiaH S, de OliveiraA C, WrightC W, FiebichB L. Anti-neuroinflammatory properties of synthetic cryptolepine in human neuroblastoma cells: possible involvement of NF-kappaB and p38 MAPK inhibition. European Journal of Medicinal Chemistry, 2013, 63 : 333– 339
CrossRef Google scholar
[21]
RasouliH, YaraniR, PociotF, Popovic-DjordjevicJ. Anti-diabetic potential of plant alkaloids: revisiting current findings and future perspectives. Pharmacological Research, 2020, 155 : 104723– 104737
CrossRef Google scholar
[22]
AblordeppeyS Y, FanP C, LiS M, ClarkA M, HuffordC D. Substituted indoloquinolines as new antifungal agents. Bioorganic & Medicinal Chemistry, 2002, 10( 5): 1337– 1346
CrossRef Google scholar
[23]
BoatengC A, ZhuX Y, JacobM R, KhanS I, WalkerL A, AblordeppeyS Y. Optimization of 3-(phenylthio)quinolinium compounds against opportunistic fungal pathogens. European Journal of Medicinal Chemistry, 2011, 46( 5): 1789– 1797
CrossRef Google scholar
[24]
ZhaoM, KamadaT, TakeuchiA, NishiokaH, KurodaT, TakeuchiY. Structure-activity relationship of indoloquinoline analogs anti-MRSA. Bioorganic & Medicinal Chemistry Letters, 2015, 25( 23): 5551– 5554
CrossRef Google scholar
[25]
SunN, DuR L, ZhengY Y, HuangB H, GuoQ, ZhangR F, WongK Y, LuY J. Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action. European Journal of Medicinal Chemistry, 2017, 135 : 1– 11
CrossRef Google scholar
[26]
GibbonsS, FallahF, WrightC W. Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta. Phytotherapy Research, 2003, 17( 4): 434– 436
CrossRef Google scholar
[27]
TuyiringireN, DeynoS, WeisheitA, ToloC U, TusubiraD, MunyampunduJ P, OgwangP E, MuvunyiC M, HeydenY V. Three promising antimycobacterial medicinal plants reviewed as potential sources of drug hit candidates against multidrug-resistant tuberculosis. Tuberculosis (Edinburgh, Scotland), 2020, 124 : 101987– 101994
CrossRef Google scholar
[28]
ChuQ R, HeY H, TangC, ZhangZ J, LuoX F, ZhangB Q, ZhouY, WuT L, DuS S, YangC J, LiuY Q. Design, synthesis, and antimicrobial activity of quindoline derivatives inspired by the cryptolepine alkaloid. Journal of Agricultural and Food Chemistry, 2022, 70( 9): 2851– 2863
CrossRef Google scholar
[29]
WiegandI, HilpertK, HancockR E. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature Protocols, 2008, 3( 2): 163– 175
CrossRef Google scholar
[30]
FanT, GuoW, ShaoT, ZhouW, HuP, LiuM, ChenY, YiZ. Design, synthesis and evaluation of phenylthiazole and phenylthiophene pyrimidindiamine derivatives targeting the bacterial membrane. European Journal of Medicinal Chemistry, 2020, 190 : 112141– 112153
CrossRef Google scholar
[31]
ChenJ, LuoY, WeiC, WuS, WuR, WangS, HuD, SongB. Novel sulfone derivatives containing a 1,3,4-oxadiazole moiety: design and synthesis based on the 3D-QSAR model as potential antibacterial agent. Pest Management Science, 2020, 76( 9): 3188– 3198
CrossRef Google scholar
[32]
YiC F, ChenJ X, WeiC Q, WuS K, WangS B, HuD Y, SongB A. α-Haloacetophenone and analogues as potential antibacterial agents and nematicides. Bioorganic & Medicinal Chemistry Letters, 2020, 30( 2): 126814– 126818
CrossRef Google scholar
[33]
KangS, KongF, ShiX, HanH, LiM, GuanB, YangM, CaoX, TaoD, ZhengY, YueX. Antibacterial activity and mechanism of lactobionic acid against Pseudomonas fluorescens and Methicillin-resistant Staphylococcus aureus and its application on whole milk. Food Control, 2020, 108 : 106876– 106885
CrossRef Google scholar
[34]
ZhaoL, DuanF, GongM, TianX, GuoY, JiaL, DengS. (+)-Terpinen-4-ol inhibits Bacillus cereus biofilm formation by upregulating the interspecies quorum sensing signals diketopiperazines and diffusing signaling factors. Journal of Agricultural and Food Chemistry, 2021, 69( 11): 3496– 3510
CrossRef Google scholar
[35]
QiL, LiH, ZhangC, LiangB, LiJ, WangL, DuX, LiuX, QiuS, SongH. Relationship between antibiotic resistance, biofilm formation, and biofilm-specific resistance in Acinetobacter baumannii. Frontiers in Microbiology, 2016, 7 : 483– 492
CrossRef Google scholar
[36]
ZhouJ W, RuanL Y, ChenH J, LuoH Z, JiangH, WangJ S, JiaA Q. Inhibition of quorum sensing and virulence in Serratia marcescens by hordenine. Journal of Agricultural and Food Chemistry, 2019, 67( 3): 784– 795
CrossRef Google scholar
[37]
BeuriaT K, SantraM K, PandaD. Sanguinarine blocks cytokinesis in bacteria by inhibiting FtsZ assembly and bundling. Biochemistry, 2005, 44( 50): 16584– 16593
CrossRef Google scholar
[38]
DomadiaP N, BhuniaA, SivaramanJ, SwarupS, DasguptaD. Berberine targets assembly of Escherichia coli cell division protein FtsZ. Biochemistry, 2008, 47( 10): 3225– 3234
CrossRef Google scholar

Acknowledgements

This work was supported financially by the National Natural Science Foundation of China (Grant Nos. 22177043 and 21877056) and the Natural Science Foundation of Gansu Province (Grant No. 20JR5RA311); the support was also supplied by the Key Program for International S&T Cooperation Projects of Gansu Province of China (Grant No. 18YF1WA115).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://dx.doi.org/10.1007/s11705-022-2196-5 and is accessible for authorized users.

RIGHTS & PERMISSIONS

2022 Higher Education Press
AI Summary AI Mindmap
PDF(12223 KB)

Accesses

Citations

Detail

Sections
Recommended

/