Combined Fourier-transform infrared imaging and desorption electrospray-ionization linear ion-trap mass spectrometry for analysis of counterfeit antimalarial tablets

This paper reports use of a combination of Fourier-transform infrared (FTIR) spectroscopic imaging and desorption electrospray ionization linear ion-trap mass spectrometry (DESI MS) for characterization of counterfeit pharmaceutical tablets. The counterfeit artesunate antimalarial tablets were analyzed by both techniques. The results obtained revealed the ability of FTIR imaging in non-destructive micro-attenuated total reflection (ATR) mode to detect the distribution of all components in the tablet, the identities of which were confirmed by DESI MS. Chemical images of the tablets were obtained with high spatial resolution. The FTIR spectroscopic imaging method affords inherent chemical specificity with rapid acquisition of data. DESI MS enables high-sensitivity detection of trace organic compounds. Combination of these two orthogonal surface-characterization methods has great potential for detection and analysis of counterfeit tablets in the open air and without sample preparation.     

Synthesis of the benzo-β-carboline isoneocryptolepine: the missing indoloquinoline isomer in the alkaloid series cryptolepine, neocryptolepine and isocryptolepine

7H-Indolo[2,3-c]quinoline has been synthesized in two steps via a new approach starting from commercially available 3-bromoquinoline and 2-bromoaniline. The new methodology consists of two consecutive palladium-catalyzed reactions: a selective Buchwald/Hartwig amination followed by an intramolecular Heck-type reaction. Alternatively, the same skeleton has also been prepared via the combination of a Suzuki arylation with an intramolecular nitrene insertion starting from 4-chloroquinoline and {2-[(2,2-dimethylpropanoyl)amino]phenyl}boronic acid. Selective methylation of 7H-indolo[2,3-c]quinoline yielded 5-methyl-5H-indolo[2,3-c]quinoline (Isoneocryptolepine) which is an interesting new lead compound in the search for new antiplasmodial drugs.     

快速诊断疟疾的免疫层析试条的研制

开发成功了一种能快速、灵敏、高特异性检测疟疾的免疫层析试条。选自恶性疟原虫富组蛋白Ⅱ－一级结构中的九肽（ＡＨＨＡＨＨＡＡＤ），经人工合成后作为免疫原，生产了一些单表位单抗；完成了一些单抗的纯化与鉴定；制取了金标单抗并对其吸收光谱进行了分析；选取了包被单抗和金标单抗间的配对；比较了影响检测的各种因子。当用此试条检测６２名已用常规血间检法确证患有疟疾个体的全血，准确率达９３．５４％。     

Synthesis and study of the antimalarial cardamom peroxide

A full account of our previously disclosed synthesis of the monoterpene dimer cardamom peroxide is reported. Inspired by hypotheses regarding the potential biosynthetic origins of this natural product, several unproductive routes are also reported. The chemical reactivity of this structurally unique metabolite in the presence of iron (II) sources is also reported as is its antimalarial activity against Plasmodium falciparum clinical isolates from several Cambodian provinces.     

Characterization of genuine and fake artesunate anti-malarial tablets using Fourier transform infrared imaging and spatially offset Raman spectroscopy through blister packs

In support of the efforts to combat the illegal sale and distribution of counterfeit anti-malarial drugs, we evaluated a new analytical approach for the characterization and fast screening of fake and genuine artesunate tablets using a combination of Raman spectroscopy, Spatially Offset Raman Spectroscopy (SORS) and Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) imaging. Vibrational spectroscopy provided chemically specific information on the composition of the tablets; the complementary nature of Raman scattering and FTIR imaging allowed the characterization of both the overall and surface composition of the tablets. The depth-resolving power of the SORS approach provided chemically specific information on the overall composition of the tablets, non-invasively, through a variety of packaging types. Spatial imaging of the tablet surface (using ATR-FTIR) identified the location of domains of excipients and active ingredients with high sensitivity and enhanced spatial resolution. The advantages provided by a combination of SORS and ATR-FTIR imaging in this context confirm its potential for inclusion in the analytical protocol for forensic investigation of counterfeit medicines.     

Bioactive compounds,anti-inflammatory,anti-nociceptive and antioxidant potentials of ethanolic leaf fraction of Sida linifolia L. (Malvaceae)

This study investigated the bioactive compounds, anti-inflammatory, anti-nociceptive, and antioxidant properties of the ethanolic leaf fraction of Sida linifolia (ELFSL). The in vitro anti-inflammatory study employed membrane stabilization, phospholipase A2, platelet aggregation, albumin denaturation, and protease inhibition assays. Intraperitoneal injection of freshly prepared carrageenan solution (0.1 mL of 0.01 g/mL), undiluted egg albumin (0.1 mL), acetic acid (0.6 % (v/v) (10 mL/kg bw), and formalin solution (0.02 mL of 1 % v/v) into mice hind paw, were used to evaluate the anti-inflammatory and anti-nociceptive mechanisms, respectively. In vitro antioxidant potentials were determined using 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO), ferric reducing power (FRAP), and total antioxidant capacity (TAC) assays. Varying quantities of flavonoids, phenols, tannins, saponins, terpenoids, steroids, and alkaloids, were detected in the fraction. GC-FID phytochemical profiling of ELFSL revealed a high level of epicatechin, moderate levels of catechin, kaempferol, flavone, naringenin, rutin flavanones, tannins, sapogenins, proanthocyanidin, and steroids, and small amounts of sparteine, resveratrol, and lunamarine. The ELFSL exerted excellent dose-dependent in vitro anti-inflammatory activities comparable with standard drugs (aspirin/prednisolone). The LD₅₀ test showed safety up to 5000 mg/kg body weight (per oral) ELFSL. Interestingly, mice pre-administered various doses (200, 400, 600 mg/kg bw, po) of ELFSL showed significant (P < 0.05) reduction in edema, writhing, and time spent licking paw in all phases compared with control and were at par with 100 mg/kg bw (po) aspirin. The result also registered good concentration-dependent antioxidant potentials for ELFSL and was comparable to standards (gallic acid, butylated hydroxytoluene, and ascorbic acid). These imply that ELFSL possesses excellent antioxidant, anti-inflammatory, and anti-nociceptive potentials mediated by peripheral and central mechanisms.     

Synthesis of 6-methyl-6H-indolo[3,2-c]isoquinoline and 6-methyl-6H-indolo[2,3-c]isoquinoline: two new unnatural isoquinoline isomers of the cryptolepine series

11H-indolo[3,2-c]isoquinoline has been synthesized in two steps starting from 4-bromoisoquinoline and 2-bromoaniline via a selective Buchwald-Hartwig reaction followed by a Pd-catalyzed intramolecular direct arylation involving C(sp²)-H activation. The synthesis of 7H-indolo[2,3-c]isoquinoline was achieved by a combination of a Suzuki reaction with an intramolecular nitrene insertion reaction starting from 4-bromoisoquinoline and {2-[(2,2-dimethylpropanoyl)amino]phenyl}boronic acid. Selective methylation of the tetracyclic skeletons yielded the title compounds 6-methyl-6H-indolo[3,2-c]isoquinoline and 6-methyl-6H-indolo[2,3-c]isoquinoline, which have never been described in the literature before.