The Anticancer Activities Phenolic Amides from the Stem of Lycium barbarum

Four new phenolic amides,4-O-methylgrossamide(1),(E)-2-(4,5-dihydroxy-2-{3-[(4-hydrox-yphenethyl)amino]-3-oxopropyl}-phenyl)-3-(4-hydroxy-3-methoxyphenyl)-N-(4-hydroxyphenethyl)acryl-amide(2),(Z)-lyciumamide C(3),(Z)-thoreliamide B(4),together with thirteen known phenolic amides were identified from the stem of Lycium barbarum.The structures of the new compounds were determined by spectroscopic methods.All compounds were evaluated for their anti-cancer activities against human glioma stem cell lines.

Novel indole and quinoline alkaloids from Melodinus yunnanensis

6/7-Seco rearranged spiro-indolone alkaloids,meloyunines A(1)and B(2)and a monoterpenoid quinoline alkaloid meloyunine C(3)together with its possible intermediate 14,15-dehydromelohenine B(4),and their precursorΔ14-vincamenine(5)were isolated from Melodinus yunnanensis.All structures were elucidated based on NMR,FTIR,UV,and MS spectroscopic data.The isolation of monoterpenoid indole,quinoline,and its immediate from the same plant chemically supported the biosynthesis of quinoline from indole.Compound 2 was cytotoxic against several human cancer cell lines.

Monoterpenoid Indole Alkaloids from Inadequately Dried Leaves of Alstonia scholaris

Six new indole alkaloids,named alstoniascholarines L–Q(1–6),together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris.Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values.In addition,the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.

Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhynchophylla were intensively reported.In current work,three new indole alkaloids(1–3),identified as geissoschizic acid(1),geissoschizic acid N4-oxide(2),and 3b-sitsirikine N4-oxide(3),as well as 26 known analogues were isolated from U.rhynchophylla.However,in the neural stem cells(NSCs)proliferation assay for all isolated compounds,geissoschizic acid(1),geissoschizic acid N4-oxide(2),isocorynoxeine(6),isorhynchophylline(7),(4S)-akuammigine N-oxide(8),and(4S)-rhynchophylline N-oxide(10)showed unexpected inhibitory activities at 10 μM.Unlike previous neuro-protective reports,as a warning or caution,our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U.rhynchophylla,while the structure–activity relationships of the isolated compounds were discussed also.

Four new isoflavanones from Tadehagi triquetrum

Four new isoflavanones with isoprenoid units,named triquetrumones E-H(1-4),were isolated from the whole plants of Tadehagi triquetrum.The structures were elucidated on the basis of spectroscopic analyses,including application of MS,UV,IR,1D and 2D NMR spectroscopic techniques.

Furostanol Saponins from Asparagus cochinchinensis and Their Cytotoxicity

Phytochemical investigation on the roots of Asparagus cochinchinensis led to the isolation of one new furostanol saponin,named 26-O-β-d-glucopyranosyl-22α-hydroxyl-(25R)-Δ5(6)-furost-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→4)]-β-d-glucopyranoside(1),along with three known congeners(2‒4).The structure of new saponin was elucidated via comprehensive inspection of its HRMS and NMR spectral data as well as chemical technology,whereas those of known ones were identified by comparison of their NMR and MS spectral data with those reported in literatures.All isolated saponins were evaluated for their cytotoxic effects on two human liver(MHCC97H)and lung adenocarcinoma(H1299)cancer cells in vitro.Among them,both 1 and 2 showed significant cytotoxicity against above mentioned cell lines.Further studies revealed that these two saponins could significantly inhibit their proliferation of MHCC97H and H1299 cells.

Monoterpenoid indole alkaloids from Alstonia rostrata

Four new monoterpenoid indole alkaloids,alstrostines C-F together with thirteen known alkaloids were isolated from the leaves and twigs of Alstonia rostrata.All structures of new compounds were elucidated based on NMR,FTIR,UV,and MS spectroscopic data.Alstrostines C-E might originate from keto-enol tautomerism of preakummicine during biogenetic pathway of akummicine.

Chemical components of Dysoxylum densiflorum

Three new diterpenoids,including two halimanes,5(10),13E-halimadiene-3α,15-diol(1),and 5(10),14-halimadiene-3α,13ξ-diol(2),one labdane,12-(3-methyl-furan)-labd-8(17)-en-19-oic acid(3),together with sixteen known compounds were isolated from the barks of Dysoxylum densiflorum.All compounds were elucidated by extensive spectroscopic analysis.

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.

Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. in Mice and Rats

Alstonia scholaris(L.)R.Br.(Apocynaceae)is an evergreen tree that has been used to treat lung diseases.In this study,the toxicity profile of indole alkaloids from leaves of A.scholaris was investigated.In acute toxicity tests,mice were adminis-tered total alkaloids(TA)and five indole alkaloids.In a chronic toxicity test,rats were continuously administered TA(50,100,and 300 mg/kg bw)for 13 weeks,followed by a 4-week recovery.A single administration of TA affected the behavior of mice,and at 12.8 g/kg bw,prone position,shortness of breath,wheezing,and convulsion were observed.The half-lethal dose(LD50)in mice was 5.48 g/kg bw,almost 2740 times the clinical dose in humans.Among the five indole alkaloids,the maximum tolerance dose in mice ranged from 0.75 to 4 g/kg bw.The TA-treated rats did not die and showed no adverse effects or dose-dependent changes in weight or food and water consumption,despite fluctuations in hematological and bio-chemical parameters compared with historical data.Furthermore,both gross and histopathological observations revealed no abnormalities in any organ.With daily oral administration to rats,the non-observed-adverse-effect-level of TA was 100 mg/kg bw.The results indicate that TA is safe for clinical use.

Indole Glycosides from Aqueous Fraction of Strychnos nitida

Three new indole glycosides 22-deoxystrictosamide(1),22-deoxystrictosamide Nb-oxide(2)and vincosamide 20-O-b-D-xylopyranoside-11-O-b-D-glucopyranoside(3),together with four known analogues were isolated from aqueous fraction of Strychnos nitida.Their structures were elucidated on the basis of extensive analysis of spectroscopic data.All the alkaloids were tested for their cytotoxic activity,but they did not show any exciting result.

Genotoxicity and Safety Pharmacology Studies of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br.

Indole alkaloids extract(IAAS)was prepared from leaves of Alstonia scholaris(L.)R.Br.,an evergreen tropical plant widely distributed throughout the world.This plant has been used historically by the Dai ethnic people of China to treat respiratory diseases.This study evaluated the genotoxicity and safety pharmacology of IAAS to support clinical use.The bacterial reverse mutation(Ames)test,in vitro mammalian chromosomal aberration test,and in vivo mammalian erythrocyte micronucleus(MN)test were performed to evaluate genotoxicity.Mice were administered IAAS(240,480,or 960 mg/kg bw)once orally to observe adverse central nervous system effects.Furthermore,beagle dogs were administered IAAS(10,30,60 mg/kg bw)once via the duodenum to evaluate its effects on the cardiovascular and respiratory systems.IAAS with or without S9-induced metabolic activation showed no genotoxicity in the Ames test up to 500μg/plate,in the mammalian chromosomal aberration test up to 710μg/mL,or in the MN test up to 800 mg/kg bw.No abnormal neurobehavioral effects were observed in mice following treatment with up to 960 mg/kg bw of IAAS.Moreover,blood pressure,heart rate,electrocardiogram parameters,and depth and rate of breathing in anesthetized beagle dogs did not differ among the IAAS doses or from the vehicle group.These data indicated that IAAS did not induce mutagenicity,clastogenicity,or genotoxicity,and no pharmaco-toxicological effects were observed in the respiratory,cardiovascular,or central nervous systems.Our results increased understanding of safety considerations associated with IAAS,and may indicate that IAAS is a possible drug candidate.

Chemistry and bioactivities of natural steroidal alkaloids

Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule.They have demonstrated a wide range of biological activities,and some of them have even been developed as therapeutic drugs,such as abiraterone acetate(Zytiga®),a blockbuster drug,which has been used for the treatment of prostate cancer.Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities,which are attractive for natural product chemistry and medicinal chemistry communities.This review comprehensively covers the structural classification,isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021,with 363 references being cited.

Anti-microbial Effects In Vitro and In Vivo of Alstonia scholaris

Alstonia scholaris could be used as a traditional medicinal plant in China for the treatment of acute respiratory,which might be caused by respiratory tract infections.The investigation tested the anti-infective effects of total alkaloids extract(TA)from leaves of A.scholaris,and as a result,TA inhibited herpes simplex virus type 1(HSV-1),respiratory syncytial virus(RSV)and influenza A virus(H1N1)in vitro respectively.In addition,the survival days of mice were prolonged,and the lung weights and mortality of mice were decreased significantly,after oral administrated TA in H1N1 and beta-hemolytic streptococcus infectious models in vivo respectively.The finding supported partly the traditional usage of A.scholaris in the treatment of respiratory infections.

Antitumor Triterpenoid Saponin from the Fruits of Avicennia marina

The fruits of Avicennia marina are widely used for both medicine and food in Guangxi of China.As a part of our continuous effort to search for bioactive molecules from the plant,the fruits of A.marina were investigated,which has led to one new triterpenoid saponin(1)and 29 known compounds been isolated and their structures were established by using spectroscopic methods and comparing with literature data.The new triterpenoid saponin showed cytotoxicity against GSC3#and GSC-18# with the IC50 values were 12.21 and 5.53 μg/mL respectively,and most of the known compounds had significant antioxidant capacity with the IC_(50) values ranging from 0.36 to 13.07 μg/mL.

Three New Pyridine Alkaloids from Vinca major Cultivated in Pakistan

Three new pyridine type alkaloids,(-)-vinmajpyridines A–C(1–3),along with two known alkaloids,have been isolated from the aerial parts of Vinca major cultivated in Pakistan.Their structures have been elucidated by means of NMR and HRESIMS spectroscopic data.The new alkaloids were evaluated for their cytotoxicity against glioma initiating cell lines(GITC-3#and GITC-18#),glioblastoma cell lines(U-87MG and T98G),and lung cancer cell line A-549,but none of them was active at 20 lg/mL concentration.

Chemical Constituents from the Stems of Ecdysanthera rosea

One new eudesmane sesquiterpenoid(1)named ecdysantherol A and two new benzene derivatives ecdysantherols B(2)and C(3),together with five known benzene derivatives(4–8)were isolated from the stems of Ecdysanthera rosea.The structures of the new compounds were elucidated by extensive spectroscopic methods and X-ray diffraction.The known compounds were identified by the comparison of their spectroscopic data with reported literature data.Compound 1 showed moderate antibacterial activity against the Providensia smartii with MIC value of 12.5 lg/mL.

Limonoid and Steroidal Saponin from Azadirachta indica

A new limonoid,17-(5-methoxy-2-oxofuran-3-yl)-28-deoxonimbolide(1),and a new C21 steroidal saponin,2a,4a-dihydroxy-pregn-5-en-16-one-3a-O-D-glucopyranoside(2),together with 11 known compounds were isolated from the methanol extract of the leaves of Azadirachta indica.The structures were elucidated by means of spectroscopic analysis and putative biosynthetic origins.All the compounds were evaluated for their antibacterial activities against six bacterial strains.

In Mourning and Memory of Late Professor Zhou Jun

Professor Zhou Jun,a world-renown natural products chem-ist,and resource botanist,passed away on March 27,2020,at the age of 89 in Kunming,China.The natural products and plant resource research field lost a noble and outstanding leader when he died since he had contributed very much to the field in a variety of aspects.He was also one of the hon-orary editors-in-chief of Natural Products and Bioprospect-ing.We deeply mourn Professor Zhou’s loss and dedicate this note to him.Professor Zhou was born on February 5,1932,in Dong-tai,Jiangsu Province,China.He started to study at the National College of Pharmacy in Nanjing in 1948.He was then educated in East China University of Chemical Tech-nology from 1954 to 1958.After he graduated,he joined to Kunming Institute of Botany,the Chinese Academy of Sciences.

Spiralosides A–C, Three New C_(27)-Steroidal Glycoalkaloids from the Fruits of Solanum spirale

Three new C_(27)-steroidal glycoalkaloids,spiralosides A–C(1–3),were obtained from the total alkaloids of Solanum spirale by chromatographic methods.On the basis of spectroscopic evidence,spiralosides A–C were elucidated as(22R,25S)-22,26-epiminocholest-5-ene-3β,16a-diol-N-acetyl-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl(1),(22R,25S)-22,26-epiminocholest-5-ene-3β,16α-diol-N-acetyl-3-O-β-D-glucopyranosyl(2),(22R,25S)-22,26-epiminocholest-3β,16α-diol-N-acetyl-3-O-β-D-glucopyranosyl(3),respectively.The total alkaloids of S.spirale have been screened for their antitussive and expectorant effects in intact animal model.