Objective:The antimicrobial activity of the ethanol extract of the Auklandia(Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.Methods:The antimicrobial a...Objective:The antimicrobial activity of the ethanol extract of the Auklandia(Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.Methods:The antimicrobial activity of the ethanol extract was tested against clinical isolates ofsome multidrug-resistant bacteria using the agar well diffusion method.Commercial antibioticswere used as positive reference standards to determine the sensitivity of the clinical isolates.Results:The extracts showed significant inhibitory activity against clinical isolates of methicillinresistantStaphylococcus aureus,Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumonia,Extended Spectrum Beta-Lactemase,Acinetobacter baumannii.The minimum inhibitory concentration values obtained using the agar dilution test ranged from 2.0μg/μL-12.0μg/μL.In the contrary the water extract showed no activity at all against the tested isolates.Furthermore,theresults obtained by examining anti-resistant activity of the plant ethanolic extract showed thatat higher concentration of the plant extract(12μg)all tested bacteria isolates were inhibited with variable inhibition zones similar to those obtained when we applied lower extract concentrationusing the well diffusion assay.Conclusion:The results demonstrated that the crude ethanolicextract of the Auklandia(Saussurea lappa)root plant has a wide spectrum of activity suggestingthat it may be useful in the treatment of infections caused by the above clinical isolates(humanpathogens).展开更多
To enhance the anti-resistance efficacy of our previously disclosed naphthyl-triazine 5,structure-based drug design strategy was rationally conducted to design a series of novel biphenyl-piperidine-triazinecontaining ...To enhance the anti-resistance efficacy of our previously disclosed naphthyl-triazine 5,structure-based drug design strategy was rationally conducted to design a series of novel biphenyl-piperidine-triazinecontaining non-nucleoside reverse transcriptase inhibitors.Remarkably,several of these compounds demonstrated single-digit nanomolar antiviral potency against both wild-type(WT)human immunodeficiency virus-1(HIV-1)and five clinically relevant mutant strains.Among these,compound 11s emerged as the most potent inhibitor,showing remarkable efficacy against WT HIV-1(50%effective concentration(EC_(50))=2 nmol/L)and five mutant strains(EC_(50)=0.003-0.073μmol/L),which was significantly superior to that of compound 5.This optimized derivative demonstrated substantially improved pharmacological properties compared to existing drugs etravirine(ETR)and rilpivirine(RPV),showing a 4-fold reduction in cytotoxicity alongside 6-fold enhancement in selectivity index(50%cytotoxic concentration(CC_(50))=19.69μmol/L,selectivity index(SI)=7438).The compound's metabolic profile revealed exceptional stability,with an elimination half-life(t_(1/2)=41.4 min)more than double that of RPV(t_(1/2)=16.03min).Comprehensive safety evaluation indicated minimal cytochrome P450(CYP)enzymes interference,low cardiac ion channel activity,and no observable acute toxicity,collectively suggesting a reduced risk profile for therapeutic applications.These promising characteristics significantly advance the development potential of biphenyl-piperidine-triazine derivatives as next-generation non-nucleoside reverse transcriptase inhibitors(NNRTIs),offering enhanced efficacy,improved safety,and favorable pharmacokinetic properties for antiretroviral therapy.展开更多
Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities agains...Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR.Compounds 7f and7 k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells（IC50;0.45,0.2μmol/L） while were much less active on A549 cancer cells（IC50;52.83,〉100μmol/L）.Both compounds could be served as promising lead compounds for further investigation.展开更多
This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics.Our endeavor involved the implementation of a bioisosterism strategy,leading to...This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics.Our endeavor involved the implementation of a bioisosterism strategy,leading to the discovery of an assemblage of halogen-containing biphenyldiarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.Notably,compound A12 demonstrated exceptional efficacy against both WT HIV-1(EC_(50)=1.9 nmol/L)and seven mutant strains(EC_(50)=1.7-157 nmol/L),surpassing that of the lead compound 6 and comparable to etravirine.Furthermore,this analog exhibited minimal adverse effects with significantly reduced cytotoxicity(CC_(50)=195μmol/L)and a high selectivity index(SI=102,608),superior to those of etravirine(CC_(50)>4.6μmol/L,SI>1436)and rilpivirine(CC_(50)=3.98μmol/L,SI=3989).It displayed low inhibition of CYP(IC_(50)=6.99-25μmol/L)and hERG(IC_(50)>40μmol/L),indicating a safer profile compared to etravirine and rilpivirine.No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg.Additionally,A12 exhibited favorable oral bioavailability(F=29.2%)and an extended elimination half-life(T _(1/2)=13.56 h),enabling convenient oral administration at minimal doses.These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.展开更多
The theoretical studies of bionics of machinery have great scientific significance,and the development of bionic machines has large practical values in the field of engineering and technology.Through the rigorous sele...The theoretical studies of bionics of machinery have great scientific significance,and the development of bionic machines has large practical values in the field of engineering and technology.Through the rigorous selection process of evolution,the survived living organisms have successfully developed outstanding abilities to adapt to their surroundings and to reproduce their offspring.In this review,we interpreted the fundamental principles of anti-adhesion and anti-resistance of soil animals by reviewing the current status in this research field and summarizing the work of the research group at Jilin University of China in the past decades.The principles and technologies used in morphology bionics,electric-osmosis bionics,flexibility bionics,configuration bionics and coupling bionics were examined.Finally,the applications of the engineering bionics and their extensive prospects were introduced.展开更多
The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-ac...The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic membranes.This study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition mechanism.OA1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme inhibition.This multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial resistance.Furthermore,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione levels.These mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.展开更多
基金Supported by the College of Medicine and Health Science,Sultan Qaboos University with the fund[Micro/Immu-Immu2013/Int/07]
文摘Objective:The antimicrobial activity of the ethanol extract of the Auklandia(Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.Methods:The antimicrobial activity of the ethanol extract was tested against clinical isolates ofsome multidrug-resistant bacteria using the agar well diffusion method.Commercial antibioticswere used as positive reference standards to determine the sensitivity of the clinical isolates.Results:The extracts showed significant inhibitory activity against clinical isolates of methicillinresistantStaphylococcus aureus,Pseudomonas aeruginosa,Escherichia coli,Klebsiella pneumonia,Extended Spectrum Beta-Lactemase,Acinetobacter baumannii.The minimum inhibitory concentration values obtained using the agar dilution test ranged from 2.0μg/μL-12.0μg/μL.In the contrary the water extract showed no activity at all against the tested isolates.Furthermore,theresults obtained by examining anti-resistant activity of the plant ethanolic extract showed thatat higher concentration of the plant extract(12μg)all tested bacteria isolates were inhibited with variable inhibition zones similar to those obtained when we applied lower extract concentrationusing the well diffusion assay.Conclusion:The results demonstrated that the crude ethanolicextract of the Auklandia(Saussurea lappa)root plant has a wide spectrum of activity suggestingthat it may be useful in the treatment of infections caused by the above clinical isolates(humanpathogens).
基金financially supported by National Natural Science Foundation of China(No.82304297)the State Key Laboratory of Natural and Biomimetic Drugs(No.K202408)。
文摘To enhance the anti-resistance efficacy of our previously disclosed naphthyl-triazine 5,structure-based drug design strategy was rationally conducted to design a series of novel biphenyl-piperidine-triazinecontaining non-nucleoside reverse transcriptase inhibitors.Remarkably,several of these compounds demonstrated single-digit nanomolar antiviral potency against both wild-type(WT)human immunodeficiency virus-1(HIV-1)and five clinically relevant mutant strains.Among these,compound 11s emerged as the most potent inhibitor,showing remarkable efficacy against WT HIV-1(50%effective concentration(EC_(50))=2 nmol/L)and five mutant strains(EC_(50)=0.003-0.073μmol/L),which was significantly superior to that of compound 5.This optimized derivative demonstrated substantially improved pharmacological properties compared to existing drugs etravirine(ETR)and rilpivirine(RPV),showing a 4-fold reduction in cytotoxicity alongside 6-fold enhancement in selectivity index(50%cytotoxic concentration(CC_(50))=19.69μmol/L,selectivity index(SI)=7438).The compound's metabolic profile revealed exceptional stability,with an elimination half-life(t_(1/2)=41.4 min)more than double that of RPV(t_(1/2)=16.03min).Comprehensive safety evaluation indicated minimal cytochrome P450(CYP)enzymes interference,low cardiac ion channel activity,and no observable acute toxicity,collectively suggesting a reduced risk profile for therapeutic applications.These promising characteristics significantly advance the development potential of biphenyl-piperidine-triazine derivatives as next-generation non-nucleoside reverse transcriptase inhibitors(NNRTIs),offering enhanced efficacy,improved safety,and favorable pharmacokinetic properties for antiretroviral therapy.
基金supported by grants from Science Foundation of Shenyang Pharmaceutical University(No.QNJJ2014502)
文摘Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR.Compounds 7f and7 k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells（IC50;0.45,0.2μmol/L） while were much less active on A549 cancer cells（IC50;52.83,〉100μmol/L）.Both compounds could be served as promising lead compounds for further investigation.
基金financially supported by National Natural Science Foundation of China(Nos.82304297 and 22077018).
文摘This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics.Our endeavor involved the implementation of a bioisosterism strategy,leading to the discovery of an assemblage of halogen-containing biphenyldiarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.Notably,compound A12 demonstrated exceptional efficacy against both WT HIV-1(EC_(50)=1.9 nmol/L)and seven mutant strains(EC_(50)=1.7-157 nmol/L),surpassing that of the lead compound 6 and comparable to etravirine.Furthermore,this analog exhibited minimal adverse effects with significantly reduced cytotoxicity(CC_(50)=195μmol/L)and a high selectivity index(SI=102,608),superior to those of etravirine(CC_(50)>4.6μmol/L,SI>1436)and rilpivirine(CC_(50)=3.98μmol/L,SI=3989).It displayed low inhibition of CYP(IC_(50)=6.99-25μmol/L)and hERG(IC_(50)>40μmol/L),indicating a safer profile compared to etravirine and rilpivirine.No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg.Additionally,A12 exhibited favorable oral bioavailability(F=29.2%)and an extended elimination half-life(T _(1/2)=13.56 h),enabling convenient oral administration at minimal doses.These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.
基金Supported by the Key Program of the National Natural Science Foundation of China(Grant Nos.50635030 and 59835200)the Chinese National Programs for Science and Technology Development(Grant No.2005BA429C)the Key Proliferation Project for Scientific and Technological Fruits of China(Grant No.2005EC000119)
文摘The theoretical studies of bionics of machinery have great scientific significance,and the development of bionic machines has large practical values in the field of engineering and technology.Through the rigorous selection process of evolution,the survived living organisms have successfully developed outstanding abilities to adapt to their surroundings and to reproduce their offspring.In this review,we interpreted the fundamental principles of anti-adhesion and anti-resistance of soil animals by reviewing the current status in this research field and summarizing the work of the research group at Jilin University of China in the past decades.The principles and technologies used in morphology bionics,electric-osmosis bionics,flexibility bionics,configuration bionics and coupling bionics were examined.Finally,the applications of the engineering bionics and their extensive prospects were introduced.
基金supported by the National Key Research and Development Program of China(2023YFD1800100 to Feng X and Bai Y)the National Natural Science Foundation of China(22177031 to Feng X,92163127 to Bai Y,82102415 to Wan M,and 82304277 to Zhang C)+4 种基金the Natural Science Foundation of Hunan Province(2024JJ4007 and 2024RC3078 to Feng X,2022RC1107 and 2024JJ2010 to Bai Y)the Natural Science Foundation of Changsha(kq2208050 to Zhang C)the Health and Medical Research Fund(HMRF),Hong Kong SAR(22210412to Wong WL)the Independent Research Project of the College of Advanced Interdisciplinary Studies of NUDT(22-ZZKY-03 to Pu H)the Project of Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs(2023TP1013)。
文摘The global antibiotic resistance crisis necessitates urgent solutions.One innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic membranes.This study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition mechanism.OA1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme inhibition.This multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial resistance.Furthermore,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione levels.These mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.
