Per- and polyfluoroalkyl substances in the atmospheric total suspended particles in Karachi, Pakistan: Profiles, potential sources, and daily intake estimates.

Per- and polyfluoroalkyl substances (PFAS) have received continuous attention; however, there is limited understanding of their sources in the atmosphere and related human exposure risks. This study measured PFAS in the atmospheric total suspended particles collected from Karachi, Pakistan, during the winter. Among the quantified PFAS, perfluorobutanoic acid (PFBA) showed the highest average concentration (3.11 ± 2.64 pg/m3), accounting for 32% of the total PFAS. Wind speed was positively correlated with perfluorohexanoic acid (PFHxA) and N-ethyl perfluorooctanesulfonamide (N-EtFOSA), while relative humidity was negatively correlated with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Weighted potential source contribution function (WPSCF) and concentration weighted trajectory (WCWT) analyses suggested that northwestern Pakistan and western Afghanistan areas were highly associated with the long-range atmospheric transport of PFAS. We also calculated the daily intake of PFAS via inhalation, which were in the range of 0.07-3.98 and 0.01-0.33 pg/kg bw/d for children and adults, respectively. The calculated hazard quotient (HQ) of PFOS and PFOA was significantly lower than 1, indicating less or unlikely to cause non-carcinogenic effect via inhalation exposure. Overall, this study contributes to the understanding of geographic origins and human inhalation risks of airborne PFAS on a regional scale.

Xanthine oxidase inhibitory activity of nicotino/isonicotinohydrazides: A systematic approach from in vitro, in silico to in vivo studies.

Change in life style and eating habits has led to an increased prevalence of hyperuricemia worldwide. The role of hyperuricemia is no more restricted to gout, but it has a central role in progression of CVD, hypertension, metabolic syndrome, and arthritis. Among the different factors involved in regulation of serum uric acid, xanthine oxidase (XO) is the best pharmacological target to control the levels of serum uric acid as it catalyzes the final steps in uric acid production. In the current study, a systemic search for the inhibitors of xanthine oxidase, starting from synthesis to in vitro screening and leading to in vivo studies is presented. Benzylidene nicotino/isonicotinohydrazides (1-54) were synthesized by treating nicotinic/isonicotinic hydrazides with substituted aromatic aldehyde, and characterized by EI-MS and 1H NMR. Elemental analysis was also performed. All synthetic compounds were screened for xanthine oxidase inhibitory activity initially using an in vitro spectroscopic XO inhibition assay. Among them twenty-two derivatives were found to be active with IC50 values between 0.96 and 330.4µM, as compared to standard drug allopurinol IC50=2.00±0.01µM. Kinetic studies of five most active compounds (8, 35, 36, 39, and 45) with low IC50 values between 0.96 and 54.8µM showed a competitive mode of inhibition. Further in silico molecular docking was carried out to study the interactions of these inhibitors with catalytically important amino acid residues in XO. Three compounds 8, 35, and 36 with IC50 values of 10, 12.4, and 0.96µM, respectively, were also found to be non-cytotoxic, and thus selected for in vivo studies. A simple and physiologically relevant animal model was used to analyze the in vivo XO inhibitory activity of these compounds. Among these, two compounds 35, and 36 showed a significant inhibition in male Wistar rats, and identified as potential lead molecules for anti-hyperuricemic drug development.

Multipathways human health risk assessment of trihalomethane exposure through drinking water.

Life-time human health risk of cancer attributed to trihalomethanes in drinking water in an urban-industrialized area of Karachi (Pakistan) was conducted through multiple pathways of exposure. The extent of cancer risk was compared with USEPA guidelines. Human health cancer risk for total trihalomethanes (TTHMs) through ingestion and dermal routes were estimated in "acceptable-low risk" (≥1.0E-06; ≤5.10E-05), whereas through inhalation route it was estimated under "acceptable-high risk" (≥5.10E-05; ≤1.0E-04) category. However, at some industrial-urban areas cancer risk for CHCl3 were estimated under "unacceptable risk" (≥1.0E-04) through inhalation route.

Three new carbazole alkaloids and biological activities of Murraya koenigii.

Three new carbazole alkaloids, mukoenigatin (1), bikoeniquinonine (2) and murrayadinal (3), were isolated from the aerial parts of Murraya koenigii, along with mukeonine-B (4). Their molecular structures were determined on the basis of spectral analysis including UV, IR, MS, and 2D NMR spectroscopy. The antimicrobial activity of different fractions of plant extract was also determined.

Antibacterial potential of Calotropis procera (flower) extract against various pathogens.

Increased bacterial resistance towards commonly used antibiotics has become a debated issue all over the world in a last few decades. Due to this, consumer demand towards natural anti-microbial agents is increasing day by day. Natural anti-microbial agents have gained enormous attention as an alternative therapeutic agent in pharmaceutical industry. Current study is an effort to explore and identify a bactericidal potential of various solvent extracts of Calotropis procera flower. Flowers of C. procera were extracted with hexane, butanol, ethyl acetate and aqua to evaluate the antibacterial activity by agar well diffusion method against the various human pathogens. The microorganisms used in this study includes Salmonella typhi, Escherichia coli (O157:H7), Micrococcus luteus KIBGE-IB20 (Gen Bank accession: JQ250612) and methicillin resistant Staphylococcus aureus (MRSA) KIBGE-IB23 (Gen Bank accession: KC465400). Zones of inhibition were observed against all four pathogenic strains. Fraction soluble in hexane showed broad spectrum of inhibition against all the studied pathogens. However, fractions soluble in ethyl acetate inhibited the growth of E. coli, MRSA, and M. luteus. In case of butanol and aqueous extracts only growth of M. luteus was inhibited. Results revealed that the flower extracts of C. procera have a potential to be used as an antibacterial agent against these pathogenic organisms.

Evaluation of the thiazole Schiff bases as ß-glucuronidase inhibitors and their in silico studies.

Twenty eight (28) derivatives 2-29 were synthesized and four analogs were found to exhibit single-digit IC(50) values as ß-glucuronidase inhibitors. Molecular modeling indicates that three factors: substituent R, lone pair on the nitrogen of azomethine part, and the interactions made by the main skeleton of the molecule, determined the enzyme inhibitory potential of these compounds. The planar conformation of the molecules allows them to fit deep inside the pocket while blocking the entry of other physiological substrates seems to play an important role in their activity.

Oxindole derivatives: synthesis and antiglycation activity.

Oxindole derivatives 3-25 have been synthesized from commercially available oxindole by refluxing with different aromatic aldehydes in good yields. Their in vitro antiglycation potential has been evaluated. They showed a varying degree of antiglycation activity with IC50 values ranging between 150.4 - 856.7 µM. 3-[(3-Chlorophenyl)methylidene]- 1,3-dihydro-2H-indol-2-one (IC50 = 150.4 ± 2.5 µM) is the most active compound among the series, better than the standard rutin with an IC50 value 294.5 ± 1.50 µM. The structures of the compounds were elucidated by 1H-NMR and mass spectroscopy and elemental analysis. A limited structure-activity relationship has been developed.

Extraction, cleanup, and chromatographic determination of imidacloprid residues in wheat.

This study presents an improved method for quantitative analysis of imidacloprid residues in wheat grain using high performance liquid chromatography. The study used chromatographic response (in terms of peak height) as a quantitative tool for determination instead of peak area. The peak height of imidacloprid showed a very good linear correlation (R(2) = 0.999) when compared with absolute values at six different concentrations. The limit of detection was found to be 0.01 µg/mL. The recovery of imidacloprid residues in spiked wheat grain at three levels (0.03, 0.05, and 0.1 µg/g) was in the range of 79%-88% with %RSD 5.72 at 0.05 µg/g (w/w) and between 87% and 93% with %RSD 3.55 at 0.1 µg/g (w/w). At 0.03 µg/g (w/w) level, recovery was not within the recommended range of 70%-110%. Therefore, the lowest limit of quantification for this method was found to be 0.05 µg/g.

Chemical constituents of Cichorium intybus and their inhibitory effects against urease and alpha-chymotrypsin enzymes.

Phytochemical investigation of the aerial parts of Cichorium intybus L. resulted in the isolation and identification of two new natural metabolites, 2,6-di[but-3(E)-en-2-onyl]naphthalene (1), and 3,3',4,4'-tetrahydroxychalcone (2), along with nine known compounds. Their structures were determined by spectroscopic techniques including 1D and 2D NMR. The known compounds were identified as scopoletin (3), 4-hydroxyphenylacetic acid (4), 3-hydroxy-4-methoxybenzoic acid (5), 4,4'-dihydroxychalcone (6), 6,7-dihydroxycoumarine (7), 1-triacontanol (8), lupeol (9), beta-sitosterol (10), and beta-sitosterol-3-O-beta-glucopyranoside (11). Compounds 4-6 and 8 are reported for the first time from C. intybus. Compounds 2 and 3 showed weak inhibitory activities against urease and alpha-chymotrypsin enzymes, respectively.

Two new coumarins from Murraya paniculata.

Two new coumarins, murrmeranzin (1) and murralonginal (2), together with four known compounds minumicrolin (3), murrangatin (4), meranzin hydrate (5) and hainanmurpanin (6) have been isolated from the aerial parts of Murraya paniculata. The structures of these compounds were determined through spectral analysis. Minumicrolin (3) showed mild butyrylcholinesterase inhibition activity.

Fluoride concentration in drinking water of Karachi city (Pakistan).

The ground and municipal water supply samples of Karachi city were analyzed for their fluoride contents. The fluoride contents in water samples collected from the subsurface and river sources were found below the WHO recommended value for the general health of the people. However, in some industrial areas the groundwater sample showed higher level of fluoride concentration. Continuous monitoring of water resources and cautious fluoridation is suggested to maintain proper status of fluoride concentration in the drinking water.