Synthesis and antitumor activity of pefloxacin C-3 methylene rhodanine devatives / 中国药科大学学报

@#To further explore an efficient strategy for the construction of antitumor fluoroquinolone molecules from antibacterial fluoroquinolone drugs, twelve new title compounds, 1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-(3-substituted-rhodanin-5-ylidene)methyl-quinolon-4(1H)-ones(6a-6l), was designed and synthesized with α, β-unsaturated ketone scaffold and a rhodanine ring as an isostere and fused modified group, respectively, from pefloxacin(1), and their structures were characterized by elemental analysis and spectral data. The in vitro anti-cell proliferative activity of the title compounds against the tested A549, Hep-3B and HL60 cancer cells exhibited more significant potency than parent 1. In particular, halogenated phenyl title compounds(6d, 6e, 6f)displayed a comparable activity to comparison doxorubicin against A549 cells and low cytotoxicity against normal Vero cells. Thus, a methylene rhodanine scaffold as a bioisostere of the C-3 carboxylic acid group have shown to be beneficial to improving the antitumor activity.

Analysis on association between incidence of hand foot and mouth disease and meteorological factors in Xiamen, 2013-2017 / 中华流行病学杂志

Objective@#To study the influence of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Xiamen, Fujian province, and provide scientific evidence for the early warning, prediction, prevention and control of HFMD.@*Methods@#Correlation analysis and distribution lag nonlinear models (DLNM) analysis of meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours and the incidence of HFMD in Xiamen during 2013 to 2017 were conducted by using R3.4.3 software.@*Results@#A total of 36 464 cases of HFMD were reported in Xiamen during 2013-2017, and the incidence showed an upward trend (F=40.359, P=0.008). The daily average relative humidity, daily average temperature and sunshine hours were positively correlated with the incidence of HFMD (r>0), and the daily average site pressure was negatively correlated with the incidence of HFMD (r<0). In the case of a lag of 0-5 days, when the daily average pressure of the station was higher than 1 005 hPa, the risk of HFMD gradually increased with the increase of air pressure, and the risk of disease decreased with the increase of lag days. The risk was highest when air pressure was 1 017 hPa and at the lag of 0 day (RR=1.14, 95%CI: 0.67-1.94). When the relative humidity was higher than 95%, the risk of HFMD gradually increased with the increase of relative humidity, and the lag time ranged from 0 day to 10 days, which was most obvious on the 4th and 5th days. The risk was highest when relative humidity was 100% and at the lag of 5 days (RR=1.32, 95%CI: 1.02-1.71). When the air temperature was >28 ℃ and <8 ℃, the risk of HFMD existed, but the lag time was inconsistent. The relative risk was highest during 15-20 days at low air temperature, and the lag time at high air temperature was mainly during 5-15 days. The risk was highest when air temperature was 28 ℃ and at the lag of 4 days (RR=1.10, 95%CI: 0.94-1.29). The sunshine time was >12 h and lag of 0-3 days was a risk factor for the incidence of HFMD. The risk was highest when sunshine time was 13 h and the lag of 0 day (RR=1.20, 95%CI: 1.05-1.36).@*Conclusion@#Meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours were associated with the incidence of HFMD with certain lag in Xiamen. So, it is suggested to use these data in the early warning system of HFMD.

Synthesis and antitumor activity of 3-(5-benzylidenethuzolo-triazlone)fluoroquinolones / 中国药科大学学报

@#To discover an efficient approach for the conversion of antibacterial fluoroquinolones into an antitumor activity, a fused heterocycle ring core, thiazolo［3, 2-b］［1, 2, 4］triazol-5-one was used as an isostere and further modified with an arylidene group. Then, 12 novel C-3 fused heterocyclic unsaturated ketones, 1- ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-［6-arylidene-thiazolo［3, 2-b］［1, 2, 4］triazol-5(6H)-one-3-yl］- quinolon-4(1H)-ones(6a-6l), were designed and synthesized from pefloxacin(1). The structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against SMMC-7721, Capan-1 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds exhibited more significantly antiproliferative activity than the parent 1. The compounds with fluorophenyl or o-methoxyphenyl showed comparable activity to the comparasion doxorubicin. Thus, it appears to be an alternative route for a fused heterocyclic unsaturated ketone as an isostere of the C-3 carboxylic group to improve the antitumor activity.

Advances in the research of long-acting strategy of insulin and GLP-1 analogs / 中国药科大学学报

@#Insulin as well as glucagon-like peptide 1(GLP-1)and its analogs are commonly used in treating type II diabetes. Both insulin and GLP-1 are endogenous peptides, and have advantages such as high efficiency and selectivity. However, there are some disadvantages to using regular insulin with slow effect, short-time effect and risk of hypoglycemia. Due to the elimination of kidneys and the metabolism of enzymes, the half-life of GLP-1 is so short that neither of them can stabilize glucose. Therefore, it is of great significance to study the long-acting strategy of insulin and GLP-1. Based on the long-acting strategy and pharmacological assessment of peptide drugs, this paper reviewed the latest progress of the related drugs that already on the market and under research to provide references for the design of novel long-acting insulin and GLP-1 analogs.

Synthesis and preliminary anti-diabetic activity evaluation of novel PEGylated GLP-1 receptor agonists / 中国药科大学学报

@#In order to obtain glucagon-like peptide-1(GLP-1)analogs which can sustainedly control the levels of glucose, 12 derivatives were designed and synthesized by coupling monomethoxy polyethylene glycol(mPEG, with average molecular weights of 350, 550 and 750)to GLP-1 analogs. Preliminary pharmacological activities showed that all compounds retained GLP-1 receptor agonist activities, and the hypoglycemic activity of compound I-12 was similar to those of Ex-4 and Liraglutide, suggesting I-12 could be a potential long-acting GLP-1 receptor agonist.

Investigation and Analysis of Parents’Cognition,Attitude and Behavior on Pediatric Medication Safety in Part of Urban Area of Fujian Province / 中国药房

OBJECTIVE:To provide reference for guaranteeing safety and rationality of pediatric medication. METHODS:Questionnaire survey was designed to investigate and analyze the cognition,attitude and behavior of parents on pediatric medication safety in urban area of Fujian province. RESULTS:Totally 1 405 questionnaires were sent out,and 1 326 were effectively received with effective rate of 94.38%. The education level of the respondents was high,and the respondents with college degree or above accounted for 57.92%. The total monthly income was also high,the respondents with monthly income of 4 000 yuan or above accounted for 61.61%. The correct answer rates of the respondents about pediatric medication safety was above 55%,but the lowest correct rate of 3 questions was only 13.73%,14.25% and 23.83%,respectively. The average score of cognition was (13.92 ± 2.80). The scores of low educational background,low monthly income and farmers were relatively low (P＜0.01). 97.06% of the respondents had trouble or difficulty in giving children drugs;the frequency of choice for children who didn’t cooperate with medication due to the taste or dosage was 29.83%;14.58% of the respondents didn’t know the accurate dosage;12.13% lacked of pediatric medication guide. 11.37%of the respondents thought that there was no drug for child specific use or not enough child-specific varieties;when children suffered from common diseases,the majority of respondents would choose municipal level or above hospitals and community health service,accounting for 49.55% and 15.46%. 85.22% of respondents had the experience of giving drug to their children by themselves. As to medication information,10.94% of respondents hold that"wanted to know but did not have the channel"and 47.66%"would read when had opportunity". 40.05% of the respondents sometimes took the initiative to consult doctor or pharmacist about pediatric medication attention,but 19.60% of respondents took little or no initiative to that. For main sources of the respondents accessing to pediatric medication guidance,the frequency of choosing doctors was 65.53%,and that of choosing pharmacists was 20.31%. 61.09% of respondents wanted to get the medication education from doctors,while 19.76% from pharmacist. Information on pediatric medication information when the respondents visited doctors and purchased drugs were also relatively simple,and were mainly about the usage and dosage. CONCLUSIONS:At present,it is common for parents to give drug to children by themselves in Fujian province. But the cognition,attitude and behavior on medication safety of children still remain to be improved. There are shortcomings in the publicity and education of knowledge and information,and the pediatric pharmaceutical care functions of pharmacists have not been fully embodied. At the same time,the development and production of children specific drugs need to be strengthened,and the information about pediatric medication in drug instructions should be standardized and improved.

Analysis on epidemiology and spatial-temporal clustering of human brucellosis in Fujian province, 2011-2016 / 中华流行病学杂志

Objective To analyze the epidemiological characteristics and spatial distribution of human brucellosis in Fujian province during 2011-2016,and provide evidence for the prevention and control of the disease.Methods The surveillance data of human brucellosis in Fujian during 2011-2016 was analyzed with software R 3.3.1,ArcGIS 10.3.1,GeoDa 1.8.8 and SaTScan 9.4.3.Results During 2011-2016,a total of 319 human brucellosis cases were reported,the incidence increased year by year (F=11.838,P=0.026) with the annual incidence of 0.14/100 000.The male to female rate ratio of the incidence was 2.50 ∶ 1.Farmers and herdsmen accounted for 57.37％.The incidence was 0.40/100 000 in Zhangzhou and 0.32/100 000 in Nanping,which were higher than other areas.The number of affected counties (district) increased from 12 in 2011 to 28 in 2016,showing a significant increase (F=13.447,P=0.021).The Moran' s I of brucellosis in Fujian between January 2011 and December 2016 was 0.045,indicating the presence of a high value or low value clustering areas.Local spatial autocorrelation analysis showed that,high-high clustering area (hot spots) were distributed in Zhangpu,Longhai,Longwen,etc,while high-low clustering areas were distributed in Nan' an and Jiaocheng,etc.Temporal scanning showed that there were three clustering areas in areas with high incidence,the most possible clustering,occurring during January 1,2013-December 31,2015,covered 6 counties,including Yunxiao,Pinghe,Longhai,etc,and Zhangpu was the center,(RR =7.96,LLR=92.62,P＜0.001).Conclusions The epidemic of human brucellosis in Fujian is becoming serious,and has spread to general population and non-epidemic areas.It is necessary to strengthen the prevention and control of human brucellosis in areas at high risk.

Analysis on epidemiology and spatial-temporal clustering of human brucellosis in Fujian province, 2011-2016 / 中华流行病学杂志

Objective To analyze the epidemiological characteristics and spatial distribution of human brucellosis in Fujian province during 2011-2016,and provide evidence for the prevention and control of the disease.Methods The surveillance data of human brucellosis in Fujian during 2011-2016 was analyzed with software R 3.3.1,ArcGIS 10.3.1,GeoDa 1.8.8 and SaTScan 9.4.3.Results During 2011-2016,a total of 319 human brucellosis cases were reported,the incidence increased year by year (F=11.838,P=0.026) with the annual incidence of 0.14/100 000.The male to female rate ratio of the incidence was 2.50 ∶ 1.Farmers and herdsmen accounted for 57.37％.The incidence was 0.40/100 000 in Zhangzhou and 0.32/100 000 in Nanping,which were higher than other areas.The number of affected counties (district) increased from 12 in 2011 to 28 in 2016,showing a significant increase (F=13.447,P=0.021).The Moran' s I of brucellosis in Fujian between January 2011 and December 2016 was 0.045,indicating the presence of a high value or low value clustering areas.Local spatial autocorrelation analysis showed that,high-high clustering area (hot spots) were distributed in Zhangpu,Longhai,Longwen,etc,while high-low clustering areas were distributed in Nan' an and Jiaocheng,etc.Temporal scanning showed that there were three clustering areas in areas with high incidence,the most possible clustering,occurring during January 1,2013-December 31,2015,covered 6 counties,including Yunxiao,Pinghe,Longhai,etc,and Zhangpu was the center,(RR =7.96,LLR=92.62,P＜0.001).Conclusions The epidemic of human brucellosis in Fujian is becoming serious,and has spread to general population and non-epidemic areas.It is necessary to strengthen the prevention and control of human brucellosis in areas at high risk.

Phenylboronic acid-based glucose-responsive materials: synthesis and applications in insulin delivery / 中国药科大学学报

Glucose-sensitive materials have attracted much interest due to their potential application in diabetes treatment in recent years.Phenylboronic acid-based glucose-responsive polymers,which possess continuous glucose sensitivity and good stability,have been most widely used in self-regulated insulin delivery.This review covers the recent advances in PBA-functionalized nanogels (microgels),micelles,vesicles and nanoparticles.Synthesis and application of these nanomaterials are discussed.With the development of PBA-regulated polymers,these nanomaterials will migrate from laboratory to clinical use in the near future.

Synthesis and antitumor activity of fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives from pefloxacin (X) / 中国药科大学学报

To explore a new strategy for further optimization to the C-3 bioisteric heterocyclic ring of fluoroquinolones,twelve novel fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives(7a-71) were designed and synthesized with both functionalized sulfanylacetic acid and Schiff-base moieties as the modified side-chain for the C-3 bioisosteric s-triazole ring of pefloxacin(1).The structures were characterized by elemental analysis and spectral data,and the in vitro anti-tumor activity of the title compounds against SMMC-7721,L1210 and HL60 cell lines was evaluated.The preliminary pharmacological results demonstrated that the title compounds possessed more significantly anti-proliferative activity than either the parent 1 or the corresponding amine intermediates(6).In particular,the title compound bearing a fluorine atom (7j) and compound bearing a nitro group attached to benzene ring (71) were comparable to the control doxorubicin against SMMC-7721 cells with an IC50 value of micro-molar concentration,respectively.It suggests that s-triazole ring modified with functional side-chain moieties instead of the C-3 carboxylic group is favorable to the improvement of antitumor activity.

Synthesis and antitumor activity of pefloxacin C-3 (rhodanine unsaturated ketone) amide derivatives / 中国药科大学学报

To explore a new strategy for the transformation of antibacterial activity of fluoroquinolone into antitumor activity,twelve new title compounds,1-ethyl-6-fluoro-7-(4-methyl-pipreazin-1-yl)-quinolin-4-one-3-carboxylicacid (5-arylidene-2-thioxo-1,3-thiozolidin-2,4-dione-3-yl) amides (6a-61),were designed and synthesized with an amide group and a rhodanine unsaturated ketone moiety as an isostere and modified group,respectively,from pefloxacin (1).Their structures were characterized by elemental analysis and spectral data.The in vitro antitumor activity of the title compounds against Hep-3B,Capan-1 and L1210 cell lines exhibited more significant potency than pefloxacin.The compounds with aromatic heterocyclic or flurophenyl displayed comparable activity to the comparasion doxorubicin.Thus,rhodanine unsaturated ketone hybrided amide group as an isostere of the C-3 carboxylic acid group appears to be an alternative route for further design of antitumor fluoroquinolone.

Investigation and Analysis for Drug Use of Children in the Township Area of Fujian Province / 中国药房

OBJECTIVE:To provide reference for the research and formulation of public health policies for children in the ru-ral area. METHODS:Questionnaire survey was designed to investigate the drug use of children in the township area of Fujian prov-ince using parents of children as subjects. RESULTS:Totally 986 questionnaires were sent out,and 969 were effectively received with effective rate of 98.28%.The education level of the respondents was low,that junior school education or below accounted for 54.49%;the respondents having trouble or difficulty in giving child drugs accounted for 97.85%;the frequency of choice for chil-dren who didn't cooperate with medication due to the taste or dosage was 17.91%;17.91% thought thatthere was not enough child-specific medication or varieties;17.71%didn't know the accurate dosage;when children suffer from common diseases,the majority of respondents would choose town clinics,accounting for 42.83%. Before giving the child drugs for the first time, 50.26% of respondents would read the instruction;16.49% of respondents couldn't understand the instruction;37.67% of respon-dentswould take the initiative to understand children's medication knowledge,22.19%wanted to know but did not have the channel,and 36.12%would read when had opportunity. 28.48%knew the difference of age and body mass in children's medi-cation,but 52.73%only had some understanding. 39.64% wanted to get the medication education from doctors,while 33.77%from pharmacist. Higher education held higher proportion on attention of children's medicine information,the extent of understand-ing children medication difference and the habit of reading drug instructions(P<0.001). CONCLUSIONS:Respondents in the town-ship have much trouble or difficulty in giving children drugs,children medication information is inadequate and inaccurate in pack-age inserts,there are many shortcomings in pharmaceutical care ability of township medical institutions,education and propaganda of rational drug use in children.

Synthesis and antitumor activities of fluoroquinolone C-3 isosteres(VIII):s-triazole sulfide-one thiosemicarbazone derivatives from pefloxacin / 中国药科大学学报

@#To improve the antitumor activity of fluoroquinolones for a promising development of druggability, twelve novel fluoroquinolone C-3 s-triazole sulfide-one thiosemicarbazone derivatives(6a-6l)were designed and synthesized with a functionalized sulfide-one thiosemicarbazone as a modified side-chain for the C-3 bioisteric s-triazole ring of pefloxacin(1). The structures were characterized by elemental analysis and spectral data。The in vitro antitumor activity of novel compounds against SMMC-7721, L1210 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds exhibited more significantly antiproliferative activity than either the parent 1 or the corresponding sulfide-one intermediates(5a-5l). In particular, compounds bearing a hydroxyl group or a fluorine atom attached to benzene ring were comparable to the control doxorubicin with an IC50 value of micro-molar concentration, respectively. It suggests that an azole ring modified with functional side-chain instead of the C-3 carboxylic group is favorable to the improve ment of antitumor activity.

Self-assembled peptide:insights and biomedicine applications / 中国药科大学学报

@#Self-assembled peptides occur via inter-molecular non-covalent assembly, spontaneity or triggering, and the formed nanostructures have been found to have certain features and functions which are not shown by the original peptide molecules or low-hierarchical molecules. There are growing attentions on the self-assembled peptide. This review provides detailed classifications of self-assembled peptides, i. e. , spontaneity and triggering, according to how the self-assemble responds or adjusts to outer environment. In addition, the summary offers potentials of their applications in biomedicine, such as anti-tumor and anti-bacterial medicine, drug carriers modifying pharmaceutical features of drugs, enhanced drug targeting, matrix as cell culture, tissue regeneration, and biomedicinal detection.

Construction and application of 3D-pharmacophore model of glucokinase agonists / 中国药科大学学报

@#Glucokinase(GK), which plays a pivotal role in maintaining glucose equilibrium in the human body, emerged as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of glucokinase agonist inhibitors have been generated with a training set of 25 glucokinase agonists(EC50 values from 2 to 78 000 nmol/L)using Discovery studio 2. 5. The best hypothesis contained three hydrogen bond acceptors, one hydrophobic center, and three excluded volumes with a correlation coefficient of 0. 955, cost difference of 60. 5, RMSD of 0. 714. This model was validated by test set, Fischer randomization test and decoy set methods. Pharmacophore model was also utilized as a three dimentional query to screen in-house andrographolide derivative database. New potential GK agonist was obtained therewith, and the hit compound is capable for further screening assay studies. Preliminary biological evaluation suggests that this new pharmacophore model fuctions superiorly in virtual screening.

Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin / 药学学报

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.

Design, synthesis, antibacterial and anti-cell proliferation activities of 1,2,4triazino3,4-h 1,8naphthyridine-8-one-7-carboxylic acid derivatives / 药学学报

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.

Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives / 药学学报

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

Synthesis and anti-proliferative activity of fluoroquinolone C-3 fused heterocyclic α,β-unsaturated ketones derived from ciprofloxacin / 药学学报

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, β-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, β-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.

Synthesis and antitumor activity of C-3 thiazolo 3 2-b 1 2 4 triazole-substituted pefloxacin derivatives / 中国药科大学学报

To search for fluoroquinolones(FQs)with antitumor activity;the C-3 carboxylic acid group of peflox-acin (1)was replaced by fused heterocyclic core;and twelve novel thiazolo[3;2-b][1;2;4]triazole heterocycles(6a-6l)were designed and synthesized.The structures of target compounds were characterized by elemental anal-ysis and spectral data.The results of the in vitro antiproliferative effect on SMMC-7721;L1210 and HL60 cell lines showed that the title compounds exhibited more significant antitumor activity than both of the pefloxacin and the corresponding opening-ring intermediates(5 a-5 l).Among them;the target compounds which possess a ben-zene ring bearing a hydroxyl group (6e)or a fluorine atom (6j)exhibited more potent antiproliferative effect on SMMC-7721 cells than other compounds.Therefore;the antitumor fluoroquinolones can be designed by replacing the C-3 carboxylic acid group of fluoroquinolones with the thiazolo[3;2-b][1;2;4]triazole moiety.