The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predomi...The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.展开更多
Objective:To investigate the content of topoisomerase I-DNA inhibitor alkaloid camptothecin(CPT) from various parts of Nothapodytes foetida(N.foetida) collected from the month of October to February.Methods:The conten...Objective:To investigate the content of topoisomerase I-DNA inhibitor alkaloid camptothecin(CPT) from various parts of Nothapodytes foetida(N.foetida) collected from the month of October to February.Methods:The content of CPT was quantified in the methanolic extract of various parts of N.foetida using high performance liquid chromatography(UPLC).Quantification was performed with the regression analysis and the method was validated as per ICH guidelines. Results:The results revealed that maximum concentrations of camptothecin were found in root(2.62%) collected in the month of February followed by fruits(January,1.22%),stem(January,0.81%) and leaves(February,0.70%).Roots were found to have 3-fold higher concentration of CPT than the leaves and stem,while the fruits showed 2-fold higher concentration.Maximum concentration of camptothecin in fruits was observed in month of January,when they were not fully mature, which was 2-fold higher than that of young and fully mature fruits.Conclusions:These findings indicate that the synthesis of CPT differs in different parts of N.foetida and the content varies periodically.展开更多
In the present investigation,we have described the green biosynthesis of silver nanoparticles(AgNPs)using ripened fruit aqueous extract of Nothapodytes nimmoniana(Graham)Mabb.as capping agent.The antioxidant,anticance...In the present investigation,we have described the green biosynthesis of silver nanoparticles(AgNPs)using ripened fruit aqueous extract of Nothapodytes nimmoniana(Graham)Mabb.as capping agent.The antioxidant,anticancer and antimicrobial activities of AgNPs were also studied.UV analysis revealed that AgNPs had a sharp peak at 416 nm.X-ray diffraction(XRD)result confirmed the characteristic peaks indicated at 111,200,220 and 311 for the crystalline of the face centered cubic silver.The Scanning Electron Microscopy analysis results confirmed the spherical shaped of AgNPs with difference sizes of the particles and an average from 44 to 64 nm.Further,fruit extract and AgNPs were evaluated total phenolic,tannin and flavonoid contents and were subjected to assess their antioxidant potential using various in vitro systems such as using 1,1-diphenyl-2-picryl-hydrazyl(DPPH),2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),metal chelating,phosphomolybdenum and ferric reducing antioxidant power(FRAP)activities and antimicrobial activity against Bacillus subtilis,Pseudomonas aeruginosa,Klebsiella pneumoniae,Staphylococcus aureus and Escherichia coli.When compared to AgNPs,fruit extract exhibited uppermost radical scavenging activities.In addition,the cytotoxicity activity was determined by MTT assay.Our results clearly proved that biosynthesized AgNPs inhibited proliferation of HeLA cell line with an IC50 of 87.32±1.43g/mL and antibacterial activity.展开更多
Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity.Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan,have been approved as potent anticancer agents,...Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity.Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan,have been approved as potent anticancer agents,there is a critical need for methods to access other aromatic ringfunctionalized congeners(e.g.,C-9,C-10,etc.).However,contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold,thereby limiting the development of modified derivatives.Reported herein,we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa,via metabolomic and transcriptomic analysis.These consist of a cytochrome P450(Nt CPT9H)which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin,as well as two methyltransferases(Nt OMT1/2,converting 9-hydroxycamptothecin to 9-methoxycamptothecin),and a uridine diphosphate-glycosyltransferase(Nt UGT5,decorating 9-hydroxycamptothecin to9-β-D-glucosyloxycamptothecin).Importantly,the critical residues that contribute to the specific catalytic activity of Nt CPT9H have been elucidated through molecular docking and mutagenesis experiments.This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering.This will hasten the discovery of novel C-9 modified camptothecin derivatives,with profound implications for pharmaceutical manufacture.展开更多
基金supported by the National Key R&D Program of China(2024YFF1306700)the Key Project of Basic Research of Yunnan Province,China(202301AS070001)the Regional Innovative Development Joint Fund of NSFC(U23A20149).
文摘The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.
基金Supported by Department of Biotechnology(DBT)research grant(Grant No.BT/PR8846/GBD/27/30/2006)
文摘Objective:To investigate the content of topoisomerase I-DNA inhibitor alkaloid camptothecin(CPT) from various parts of Nothapodytes foetida(N.foetida) collected from the month of October to February.Methods:The content of CPT was quantified in the methanolic extract of various parts of N.foetida using high performance liquid chromatography(UPLC).Quantification was performed with the regression analysis and the method was validated as per ICH guidelines. Results:The results revealed that maximum concentrations of camptothecin were found in root(2.62%) collected in the month of February followed by fruits(January,1.22%),stem(January,0.81%) and leaves(February,0.70%).Roots were found to have 3-fold higher concentration of CPT than the leaves and stem,while the fruits showed 2-fold higher concentration.Maximum concentration of camptothecin in fruits was observed in month of January,when they were not fully mature, which was 2-fold higher than that of young and fully mature fruits.Conclusions:These findings indicate that the synthesis of CPT differs in different parts of N.foetida and the content varies periodically.
文摘In the present investigation,we have described the green biosynthesis of silver nanoparticles(AgNPs)using ripened fruit aqueous extract of Nothapodytes nimmoniana(Graham)Mabb.as capping agent.The antioxidant,anticancer and antimicrobial activities of AgNPs were also studied.UV analysis revealed that AgNPs had a sharp peak at 416 nm.X-ray diffraction(XRD)result confirmed the characteristic peaks indicated at 111,200,220 and 311 for the crystalline of the face centered cubic silver.The Scanning Electron Microscopy analysis results confirmed the spherical shaped of AgNPs with difference sizes of the particles and an average from 44 to 64 nm.Further,fruit extract and AgNPs were evaluated total phenolic,tannin and flavonoid contents and were subjected to assess their antioxidant potential using various in vitro systems such as using 1,1-diphenyl-2-picryl-hydrazyl(DPPH),2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),metal chelating,phosphomolybdenum and ferric reducing antioxidant power(FRAP)activities and antimicrobial activity against Bacillus subtilis,Pseudomonas aeruginosa,Klebsiella pneumoniae,Staphylococcus aureus and Escherichia coli.When compared to AgNPs,fruit extract exhibited uppermost radical scavenging activities.In addition,the cytotoxicity activity was determined by MTT assay.Our results clearly proved that biosynthesized AgNPs inhibited proliferation of HeLA cell line with an IC50 of 87.32±1.43g/mL and antibacterial activity.
基金supported by National Natural Science Foundation of China(82225043)Biological Resources Program(KFJBRP-009)+1 种基金Yunnan Revitalization Talent Support Program“Yunling Scholar”Project(S.-X.H.)Yunnan Revitalization Talent Support Program“Young Talent”Project(J.-P.H.)。
文摘Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity.Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan,have been approved as potent anticancer agents,there is a critical need for methods to access other aromatic ringfunctionalized congeners(e.g.,C-9,C-10,etc.).However,contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold,thereby limiting the development of modified derivatives.Reported herein,we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa,via metabolomic and transcriptomic analysis.These consist of a cytochrome P450(Nt CPT9H)which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin,as well as two methyltransferases(Nt OMT1/2,converting 9-hydroxycamptothecin to 9-methoxycamptothecin),and a uridine diphosphate-glycosyltransferase(Nt UGT5,decorating 9-hydroxycamptothecin to9-β-D-glucosyloxycamptothecin).Importantly,the critical residues that contribute to the specific catalytic activity of Nt CPT9H have been elucidated through molecular docking and mutagenesis experiments.This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering.This will hasten the discovery of novel C-9 modified camptothecin derivatives,with profound implications for pharmaceutical manufacture.
