NMR-based metabolic profiling for serum of mouse exposed to source water

¹H nuclear magnetic resonance (NMR) based metabonomic method was used to characterize the profile of low-molecular-weight endogenous metabolites in mouse (Mus musculus) serum following exposure to Taihu Lake source water for 90 days. The ¹H NMR spectra of mice sera were recoded and a total of 21 metabolites were identified. Data reduction and latent biomarkers identification were processed by pattern recognition (PR) analysis. The principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) identified differences in metabolic profiles between control and treatment groups. A number of serum metabolic perturbations were observed in sera of source water treatment mice compared to control mice, including decreased levels of acetone, pyruvate, glutamine, lysine and citrate. These results indicated that Taihu Lake source water could induce energy metabolism changes in mouse related to fatty acid β-oxidation, tricarboxylic acid (TCA) cycle, citric acid cycle, and metabolism of some amino acids. ¹H NMR-based metabolic profiling provides new insight into the toxic effect of Taihu Lake source water, and suggests potential biomarkers for noninvasive monitoring of health risk.     

Comparative studies on the nephrotoxicity of 2-bromoethanamine hydrobromide in the Fischer 344 rat and the multimammate desert mouse (Mastomys natalensis)

Renal papillary necrosis (RPN) was induced in Fischer 344 (F344) rats (n=4) using 2-bromoethanamine hydrobromide (BEA) dosed at 150 mg/kg, and in multimammate desert mice (Mastomys natalensis) at 150 and 250 mg/kg (n=4) per group). Control rats andMastomys were dosed with 0.9% saline (n=4 per group). Urine was collected at regular intervals for up to 4 days post-dosing and analysed for low MW metabolites using high resolution¹H NMR spectroscopy. The urinary activity of lactate dehydrogenase, γ-glutamyl transpeptidase and alkaline phosphatase was determined using conventional biochemical assays. On termination, histopathological examination of papillae was performed showing the development of extensive lesions in F344 rats at 150 mg/kg BEA.Mastomys appeared much more resistant to BEA and showed normal renal histology at 150 mg/kg and patchy lesions at 250 mg/kg BEA. Enzyme analysis of control urine showed F344 rats to have > 1000% higher γ-glutamyl transpeptidase activity thanMastomys.¹H NMR spectroscopic analysis showed that BEA caused a substantial decrease in urinary concentrations of succinate and citrate (0–24 h p.d.) and an increase in creatine (0–96 h p.d.) in both animal models. A decrease in the urinary concentration of 2-oxoglutarate with a subsequent increase by 72–96 h p.d. was also noted in both animal models. Glutaric and adipic aciduria were also induced in both F344 rats andMastomys 0–24 h post-BEA treatment, indicative of an enzyme deficiency in the acyl CoA dehydrogenases. Urinary taurine levels were elevated inMastomys following the administration of BEA, indicating some degree of liver toxicity. Urinary taurine was not elevated in F344 rats following BEA administration, demonstrating further species difference in BEA toxicity.     

Bacopa monniera exerts antiamnesic effect on diazepam-induced anterograde amnesia in mice

Rationale  As Benzodiazepines are known to produce amnesia by involvement of the GABAergic system, we examined Bacopa monniera, an herb known for memory enhancement for reversal of memory deficits caused by diazepam. Objectives  The objective of the study was to study the effect of standardized extract of B. monniera on diazepam-induced amnesia in mice using Morris water maze. Materials and methods  We used the rota rod test as a screening measure for muscle incoordination followed by the Morris water maze scale to evaluate the effect of B. monniera on amnesia. The index of acquisition and retrieval was recorded with varying doses of Bacopa. Results  The results revealed antiamnesic effects of B. monniera (120 mg kg⁻¹ oral) on diazepam (1.75 mg kg⁻¹ intraperitoneal)-induced amnesia. The degree of reversal by Bacopa was significant as it progressively reduced escape latency time when mice treated with diazepam were subjected to acquisition trials. Conclusions  The antiamnesic effects of Bacopa suggest likely a gamma-aminobutyric acid–benzodiazepine pathway possibly affecting long-term potentiation. Sudesh Prabhakar and Manish Kumar Saraf: Equal authorship     

Evaluation of genotoxicity and effects on reproduction of nonylphenol in <Emphasis Type="Italic">Oreochromis niloticus</Emphasis> (Pisces: cichlidae)

Nonylphenol ethoxylate (NPE) is widely used as a component of detergents, paints, pesticides, and many other products. In the aquatic environment NPE breakdown to 4-nonylphenol (NP), which is more stable and persistent. NP is estrogenic in fish, avian, and mammals and is described as an environmental pollutant with endocrine disruptor characteristics. The genotoxicity of NP was evaluated through micronuclei assay and single cell gel electrophoresis (Comet assay) in peripheral erythrocytes of Oreochromis niloticus exposed in vivo. The study on reproductive development was also carried out in male and female gonads of O. niloticus. Lethal concentration (LC 50%) of 0.032 ml l⁻¹ was previously determined. We ran assays with O. niloticus exposed to concentrations of 1.0, 10.0, and 16.0 μl l⁻¹ of NP diluted in water. Our results showed that NP was not genotoxic. However, 3-day exposure to NP in concentrations of 1.0, 10.0, and 16.0 μl l⁻¹ of water increased the frequency of reproductive stages in males and females. The histology of the reproductive tract of the treated fish was significantly altered in females treated with 16.0 μl l⁻¹ of water when compared to controls. Analogous estrogenic effects were observed, such as accelerated maturation of oocytes and spermatogenesis. These results showed that the O. niloticus reproductive system is sensitive to NP estrogenicity.     

Quantitative determination of atractylon in Atractylodis Rhizoma and Atractylodis Lanceae Rhizoma by <Superscript>1</Superscript>H-NMR spectroscopy

¹H-NMR spectroscopy was successfully applied to the quantitative determination of atractylon in Atractylodis Rhizoma (dried rhizomes of Atractylodes ovata and A. japonica) and Atractylodis Lanceae Rhizoma (dried rhizomes of Atractylodes lancea and A. chinensis). The analysis was carried out by comparing the integral of the H-12 singlet signal of atractylon, which was well separated in the range of δ 6.95–7.05 ppm in the NMR spectrum, with the integral of a hexamethyldisilane (HMD) signal at δ 0 ppm. The atractylon contents obtained by the ¹H-NMR spectroscopy were consistent with those obtained by the conventional HPLC analysis. The present method requires neither reference compounds for calibration curves nor sample pre-purification. It also allows simultaneous determination of multiple constituents in a crude extract. Thus, it is applicable to chemical evaluation of crude drugs as a powerful alternative to various chromatographic methods.     

Toxicity of the amphoteric surfactant, cocamidopropyl betaine, to the marine macroalga, Ulva lactuca

The degradation of the synthetic, amphoteric surfactant, cocamidopropyl betaine (CAPB) and its toxicity to the marine macroalga, Ulva lactuca, has been evaluated using several different physiological test end-points over different periods of exposure up to 120 h. Droplet surface angle measurements revealed that, following a period of acclimation of about 24 h, CAPB began to degrade and that primary degradation was complete within 120 h. Effective quantum yield (∆F/F_m′) and relative growth rates (RGRs) were the most sensitive measures of phytotoxicity, with CAPB concentrations at and above 10 mg l⁻¹ eliciting irreversible, time-dependent and/or dose-dependent responses. Cell membrane damage, estimated from measurements of ion leakage, was detected only at a concentration of 40 mg l⁻¹ after 48 h of exposure to CAPB but by 120 h damage was evident at all measured concentrations above 10 mg l⁻¹. These observations suggest that both CAPB and its metabolites are intrinsically toxic to U. lactuca. The findings of this study are discussed in terms of the environmental consequences of applying CAPB to control harmful algal blooms.     

Chronic exposure to pentavalent arsenic of larval leopard frogs (Rana pipiens): bioaccumulation and reduced swimming performance

Arsenic (As) is mainly released to the environment from anthropogenic sources, with inorganic pentavalent As (As [V]) predominant in surface water. In this study, Rana pipiens were exposed to As (V) in water at environmentally relevant concentrations (control, 10, 20, 150, 500, and 1,000 μg l⁻¹) in a static-renewal system from post-hatch stage through metamorphosis for 113 days. There was no significant effect of As exposure on tadpole survival, growth, and percent metamorphosis. Maximum swimming speed was significantly slower in the As-treated groups compared with the control. During the period of tail resorption (Gosner stage 42–46), no significant differences in age at metamorphosis, survival, length of tail resorption period, snout-vent length of metamorphs, and sex ratio were found among treatments. Whole body As concentrations ranged from <0.6 to 5.31 mg kg⁻¹ dry mass, and were significantly higher in the 150, 500, and 1,000 μg l⁻¹ treatments than the control. Based on our data, larval tissue concentrations of As close to that reported in previous field studies were not associated with any significant effects except decreased tadpole swimming speed.     

Change in life cycle parameters and feeding rate of <Emphasis Type="Italic">Ceriodaphnia silvestrii</Emphasis> Daday (Crustacea,Cladocera) exposure to dietary copper

Changes in life cycle parameters (survival, growth, reproduction) and feeding rate of the tropical cladoceran Ceriodaphnia silvestrii as affected by Cu contaminated algae Pseudokirchneriella subcapitata were investigated. The dietary copper exposure ranged from 3 × 10⁻¹⁵ to 68 × 10⁻¹⁵ g Cu algal cell⁻¹. Low waterborne copper exposure (around 10⁻¹⁰ mol l⁻¹ free Cu²⁺ ions) was kept in the experiments. The results show an increasing toxic effect on C. silvestrii with copper increase in algal cells; at the highest copper exposure, all life cycle parameters were significantly affected. A concentration of 38 × 10⁻¹⁵ g Cu algal cell⁻¹ reduced egg hatching percentile and the number of neonates produced per female, but did not cause any statistically significant effect on animals survival nor to the number of eggs produced per female. The following sequence of events was observed from the lowest to the highest copper contamination: reproduction, feeding rate, body length and, at last, survival was affected. We conclude that algal cells are an important route of copper exposure and toxicity to cladocerans.     

Anticomplementary activity of ergosterol peroxide fromNaematoloma fasciculare and reassignment of NMR data

A very high content (at least 0.23%) of ergosterol peroxide was isolated fromNaematoloma fasciculare Karst. Not only ergosterol peroxide but also ergosterol showed very strong anticomplementary activity on the classical pathway, the IC₅₀ values being 5.0 μM and 1.0 μM, respectively. The¹H and¹³C NMR data of ergosterol peroxide were revised and completely assigned by DEPT,¹H-¹H COSY, HMQC and HMBC correlations.     

Investigating glucosyltransferase inhibitory activities of polyphenols from kapur (<Emphasis Type="Italic">Dryobalanops</Emphasis> sp.) heartwood extracts

The inhibitory effects of 50% aqueous ethanol extracts obtained from 36 tropical woody plants species on glucosyltransferase (GTase) activity were studied. Out of the 36 species examined, those obtained from kapur (Dryobalanops sp.), a species growing in Kalimantan (Indonesia), showed the highest level of GTase inhibition. Kapur extracts were further subjected to fractionation using column chromatography (LH-20 gel, cellulose and C-18 silica gel column). LH-20 gel provided the most successful method of fractionation. The separated fractions showed positive with Folin-Ciocalteau’s reagent and negative with vanillin-HCl reagent, indicating that the main constituents of the active fractions were polyphenols but not proanthocyanidin (condensed tannins). Results of the assay for protein precipitating ability with bovine serum albumin (BSA) solution suggested these polyphenols have strong protein-precipitating ability. The predominant compound produced after acid hydrolysis was ellagic acid, indicating that the GTase-inhibitory components were mainly ellagitannins. Two polyphenolic compounds referred to as compounds 1 and 2 were isolated from the water eluate fraction with LH-20 gel column, and these compounds showed comparatively strong GTase-inhibitory activities and relatively low molecular weight. Using a combination of two-dimensional, ¹H and ¹³C nuclear magnetic resonance analysis, compound 1 was identified as 4-methoxy-2-[tetrahydro-3,4,5-trihydroxy-6-(hydroxymethyl)pyran-2-yl]-α-resorcylic acid δ–lactone (bergenin), and 2 was identified as 4-O-(α-rhamnopyranosyl) ellagic acid (eschweilenol C). Bergenin has been previously isolated from the roots of Bergenia crassifolia, and eschweilenol C has been isolated from the bark of Eschweilera coriacea. Both compounds were found in kapur for the first time.     

Subchronic cadmium exposure upregulates the mRNA level of genes associated to hepatic lipid metabolism in adult female CD1 mice

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in humans and shows adverse effects on health. Accumulating evidence reveals that environmental Cd exposure is associated with hepatic lipid accumulation and metabolic alterations in adult male mice. However, whether Cd exposure induces hepatic lipid accumulation and metabolic alterations in female mice remains poorly understood. In the present study, we aimed to investigate the effects of Cd exposure on insulin resistance, hepatic lipid accumulation and associated metabolic pathways. Female CD1 mice were administrated with CdCl₂ (10 and 100 mg l^–1) by drinking water. We found that Cd exposure did not induce obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in the Cd‐100 mg l^–1 group presented a significant reduction of the glucose area under the curve during the glucose tolerance test. However, there was a significant elevation in the mRNA level of Fasn and Scd‐1, which were critical genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two genes for hepatic fatty acid uptake were upregulated in Cd‐treated mice. Of interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in Cd‐treated mice. Collectively, our results suggest that Cd exposure upregulated mRNA level of genes related to hepatic lipid metabolism although there was no insulin resistance and hepatic lipid accumulation shown in the present study.     

山药提取物联合树突细胞-细胞因子诱导的杀伤细胞对荷MDA-MB-231乳腺癌干细胞瘤裸鼠的治疗作用研究

目的 研究山药Dioscorea opposita提取物联合树突细胞-细胞因子诱导的杀伤细胞（DC-CIK）对荷MDA-MB-231乳腺癌干细胞瘤裸鼠的治疗效果。方法 制备荷MDA-MB-231乳腺癌干细胞Balb/c裸鼠模型,随机分为4组,每组8只：对照组裸鼠尾iv生理盐水,0.2 mL/次,2次/周;DC-CIK组裸鼠在肿瘤干细胞接种4 d后尾iv 1×10⁶个DC-CIK细胞,2次/周,给药3周;山药提取物组裸鼠ig山药提取物125 mg/kg,0.2 mL/d,给药3周;山药提取物联合DC-CIK组裸鼠ig山药提取物125 mg/kg,0.2 mL/d,同时尾iv 1×10⁶个DC-CIK细胞,2次/周,给药3周。各组裸鼠在治疗3周期间每2天测量瘤体大小及裸鼠体质量,治疗结束后处死裸鼠,取出瘤体称质量;qRT-PCR法检测瘤组织中Akt信号通路中关键原癌基因c-Myc表达水平。结果 治疗结束后,各组裸鼠瘤体生长速率为山药提取物联合DC-CIK组结论 对荷MDA-MB-231乳腺癌干细胞瘤裸鼠治疗效果中,各给药组裸鼠肿瘤生长均受到明显抑制,其中以山药提取物联合DC-CIK组效果最佳。     

Nickel and phosphorous sorption efficiencies, tissue accumulation kinetics and morphological effects on Eichhornia crassipes

The aim of the research was to assess the uptake efficiencies of Ni and P, their distribution in tissues along time and their toxic effects on the internal and external morphologies of Eichhornia crassipes. Aquaria with plants exposed to 1 mg Ni l⁻¹ or 5 mg P l⁻¹ and control were arranged in triplicate. Water and plants (aerial parts and roots) were sampled along 30 days. Ni uptake and tissue bioaccumulation kinetics was significantly faster than that of P. Mean root length, number of leaves, biomass and chlorophyll concentration were negatively affected by Ni, while these parameters were significantly increased by P in comparison with the control. Stele and metaxylem vessel cross-sectional areas (CSA) in the P treatment were significantly lower in comparison with that obtained in the Ni treatment and in control. Metaxylem vessels CSA in plants exposed to Ni were significantly higher while the number of vessels was significantly lower than those obtained in the control. Despite the toxic effects, E. crassipes efficiently accumulated Ni, probably due to the morphological plasticity of its root system.     

不同比活度11C-氟马西尼体内代谢的差异分析

目的 通过测定¹¹C-氟马西尼（¹¹C-flumazenil,¹¹C-FMZ）在体内主要代谢物的百分占比,分析不同比活度¹¹C-FMZ的代谢差异。方法 选取2019年5月至10月10名受试者,其中,男性5名,女性5名,平均年龄（41.7±4.7）岁,平均体重（69.3±6.8）kg。先后注射高低两种比活度（268.3±57.2）×10³和(57.8±11.4)×10³Ci/mol的¹¹C-FMZ,并分别测定注射后1、2、3、4、5、10、15、20、30、40、60 min时血浆中¹¹C-FMZ及其代谢物的百分注射剂量率,使用配对样本均数t检验计算并对比两组代谢物的百分占比。结果 代谢物的百分占比随时间逐步增加,于15 min后基本趋于稳定,且低比活度组的百分占比明显高于高比活度组,在15～60 min的区间存在显著统计学差异（P<0.05）。结论 不同比活度的¹¹C-FMZ注射后的代谢率存在明显差异,临床应用时应尽量避免比活度差异过大。     

An Investigation into the Rheology of Pharmaceutical Inter-granular Material Bridges at High Shear Rates

Purpose  This study was undertaken to investigate the rheological properties of inter-granular material bridges on the nano-scale when strained at high shear rates. Materials and Methods  Atomic force microscopy (AFM) was used as a rheometer to measure the viscoelasticity of inter-granular material bridges for lactose:PVP K29/32 and lactose:PVP K90 granules, produced by wet granulation. Results  The loss tangent (tan δ) and both the storage (G′) and loss shear moduli (G″) of inter-granular material bridges were measured as a function of the probe–sample separation distance, oscillation frequency and relative humidity (RH). As the probe was withdrawn from the granule surface tan δ initially increased rapidly from zero to a plateau phase. G″ became increasingly dominant as the bridge was further extended and eventually exceeded G′. At high RH, capillary forces were foremost at bridge rupture, whereas at low RH elastic forces dominated. The effect of increasing frequency was to increase the effective elasticity of the bridge at high RH. Conclusions  AFM has been employed as a rheometer to investigate the nano-scale rheology of inter-granular material bridges. This novel method may be used to obtain a fundamental understanding how different binders, granulated with different diluent fillers, behave at high shear rates.     

灵芝孢子油、破壁灵芝孢子粉及灵芝孢子提取物对小鼠急性胃溃疡的保护作用

目的 探讨灵芝孢子油、破壁灵芝孢子粉及灵芝孢子提取物对小鼠急性胃溃疡的影响。方法 雄性ICR小鼠随机分为12组：对照组,模型组,奥美拉唑（阳性药,4 mg·kg^-1）组,灵芝孢子提取物低、中、高剂量（0.2、0.4、0.8 g·kg^-1）组,破壁灵芝孢子粉低、中、高剂量（0.6、1.2、2.4 g·kg^-1）组,灵芝孢子油低、中、高剂量（0.2、0.4、0.8 g·kg^-1）组,每组20只。ig给药,每天1次,对照组和模型组给予等体积的生理盐水。连续给药7 d后,禁食12 h,除对照组外,每组随机选取10只小鼠ig无水乙醇（10 mL·kg^-1）建立急性胃溃疡模型,1.5 h后取材;每组余下10只小鼠ig吲哚美辛（40 mg·kg^-1）建立急性胃溃疡模型,3 h后取材。观察小鼠的一般状况、胃出血和溃疡情况,进行胃损伤评分,计算损伤抑制率和损伤发生率。结果 各组小鼠给药过程中无异常。小鼠给予无水乙醇后,模型组和奥美拉唑组10 min后开始出现行动变缓,肢体活动不协调,呼吸加深、频率减慢等症状,而给予灵芝孢子提取物、破壁灵芝孢子粉和灵芝孢子油的小鼠在30 min后才陆续出现症状;给予吲哚美辛的小鼠自主活动减少,各组之间无差别;对照组小鼠行为活动如常。与对照组比较,小鼠经无水乙醇、吲哚美辛ig导致非常明显的胃溃疡,胃损伤评分显著升高（P<0.01）,损伤发生率为100%;与模型组比较,预防性给予灵芝孢子提取物、破壁灵芝孢子粉、灵芝孢子油可明显降低胃出血或溃疡等胃黏膜损伤,其中灵芝孢子提取物高剂量组、破壁灵芝孢子粉组、灵芝孢子油组的胃损伤评分显著降低（P<0.01）,损伤抑制率显著提高（P<0.01）,损伤发生率明显降低。结论 灵芝孢子油、破壁灵芝孢子粉及灵芝孢子提取物能有效抑制小鼠急性胃溃疡的发生,灵芝孢子油效果最佳,破壁灵芝孢子粉次之,并且对于无水乙醇导致的急性胃溃疡抑制作用尤为显著。     

构树总黄酮对免疫抑制小鼠免疫功能的影响

目的 探讨构树总黄酮（total flavonoids of Broussonetia papyrifera,TFBP）对环磷酰胺诱导的免疫抑制小鼠免疫功能的影响。方法 用环磷酰胺复制免疫抑制模型并随机分为模型组、构树总黄酮高、中、低剂量组（200,100,50 mg·kg^-1·d^-1）,以正常小鼠为空白对照组。分别于饲喂构树总黄酮后第10天和第30天采样,检测白细胞含量、腹腔巨细胞吞噬功能、T、B淋巴细胞转化率、血清IgG含量及BSA抗体水平。结果 与模型组比较,饲喂TFBP的高、中、低剂量组小鼠的白细胞含量、腹腔巨噬细胞吞噬功能、T、B淋巴细胞转化率、BSA抗体水平和血清IgG均显著升高（P < 0.05或P < 0.01）,随着TFBP剂量的增加,上述免疫指标与空白对照组相近。结论 构树总黄酮能显著改善环磷酰胺诱导的免疫抑制小鼠的免疫功能。     

基于皮肤外燥模型小鼠的干燥皮肤综合评价及银耳多糖的干预研究

目的 制备皮肤外燥模型小鼠,对小鼠皮肤进行综合评价并研究银耳多糖内服、外用的干预作用。方法 10只KM小鼠置于人工气候箱内按“温度-湿度-风”综合条件建立皮肤外燥小鼠模型;另90只KM小鼠,除空白组常规饲养,其余各组按外燥造模条件饲养。银耳多糖的干预研究分为内服和外用,内服给药动物随机分为空白组、模型组（等量生理盐水）和银耳多糖组（400,200,100 mg·kg^-1）;外用给药动物分为经皮空白组、经皮模型组（等量生理盐水）、经皮银耳多糖组（银耳多糖10 mg·cm^-2）和阳性对照组[透明质酸（hyaluronic acid,HA）10 mg·cm^-2],每日1次,连续给药20 d。观测不同给药方式在银耳多糖干预下小鼠皮肤表观特征、含水量、组织结构、HA含量以及水通道蛋白3（aquaporin-3,AQP3）表达量的影响。结果 皮肤综合评价结果表明,外燥模型建立成功;在银耳多糖干预下,与空白组比较,内服与外用给药的模型组皮肤含水量、HA含量以及AQP3表达量降低（P<0.05）;与模型组相比,各给药组可显著提高皮肤含水量、HA含量以及AQP3表达量（P<0.05）,且内服以银耳多糖高剂量组效果最好（P<0.05）,外用经皮银耳多糖组效果优于阳性对照组（P<0.05）。各给药组较模型组皮肤恢复色泽,未见明显皮屑与裂纹,毛发可正常增长,皮肤组织结构相对完整,毛囊与皮脂腺数目增多。结论 外燥可致皮肤干燥的理论成立。银耳多糖对皮肤外燥模型小鼠内服外用具有延缓干燥的功效,其作用可能与银耳多糖调节皮肤HA和AQP3表达量相关。     

Synthesis, characterization, antibacterial, antifungal, and immunomodulating activities of gatifloxacin derivatives

Gatifloxacin is a synthetic broad-spectrum fluorquinolone antibacterial agent with a 3-methylpiperazinyl-side chain at position 7 and a methoxy group at position 8 of the quinolone ring. In the present study different analogues of gatifloxacin were prepared; the piperazinyl ring was chosen as the center of reaction for synthesizing this series of derivatives. The structures of these derivatives were established using spectroscopic techniques such as IR, ¹H NMR, and EIMS. In vitro antibacterial and antifungal activities were evaluated by disc diffusion method and these derivatives were compared with in-use fluoroquinolones like gatifloxacin, sparfloxacin, and gemifloxacin. Derivative A proved very potent against Gram-negative organisms, especially Pseudomonas aeruginosa, Shigella flexeneri, and Klebseilla pneumoniae, and derivatives A–C exhibited good antifungal activity compared to in-use quinolones. In addition, gatifloxacin and derivatives were investigated for immunomodulating activities. Derivative B has good anti-inflammatory activity, with IC₅₀ < 12.5 μg/ml.