Carbon footprint of synthetic nitrogen under staple crops: A first cradle-to-grave analysis.

More than half of the world's population is nourished by crops fertilized with synthetic nitrogen (N) fertilizers. However, N fertilization is a major source of anthropogenic emissions, augmenting the carbon footprint (CF). To date, no global quantification of the CF induced by N fertilization of the main grain crops has been performed, and quantifications at the national scale have neglected the CO2 assimilated by plants. A first cradle-to-grave life cycle assessment was performed to quantify the CF of the N fertilizers' production, transportation, and application to the field and the uses of the produced biomass in livestock feed and human food, as well as biofuel production. We quantified the direct and indirect inventories emitted or sequestered by N fertilization of main grain crops: wheat, maize, and rice. Grain food produced with N fertilization had a net CF of 7.4 Gt CO2eq. in 2019 after excluding the assimilated C in plant biomass, which accounted for a quarter of the total CF. The cradle (fertilizer production and transportation), gate (fertilizer application, and soil and plant systems), and grave (feed, food, biofuel, and losses) stages contributed to the CF by 2%, 11%, and 87%, respectively. Although Asia was the top grain producer, North America contributed 38% of the CF due to the greatest CF of the grave stage (2.5 Gt CO2eq.). The CF of grain crops will increase to 21.2 Gt CO2eq. in 2100, driven by the rise in N fertilization to meet the growing food demand without actions to stop the decline in N use efficiency. To meet the targets of climate change, we introduced an ambitious mitigation strategy, including the improvement of N agronomic efficiency (6% average target for the three crops) and manufacturing technology, reducing food losses, and global conversion to healthy diets, whereby the CF can be reduced to 5.6 Gt CO2eq. in 2100.

Blood pH and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide war. Raising the blood pH might be a crucial strategy to chase COVID-19. The human blood is slightly alkaline, which is essential for cell metabolism, normal physiology, and balanced immunity since all of these biological processes are pH-dependent. Varieties of physiologic derangements occur when the blood pH is disrupted. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proliferates in acidic blood that magnifies the severity of COVID-19. On the other side, blood acidemia is linked to increased morbidity and mortality because of its complications on immunity, especially in the elderly and in critical diseases such as cancer, musculoskeletal degradation, renal, cardiac, and pulmonary disorders, which result in many pathological disorders such as osteomalacia, and disturbing the hematopoiesis. Additionally, acidemia of the blood facilitates viral infection and progression. Thus, correcting the acid-base balance might be a crucial strategy for the treatment of COVID-19, which might be attributed to the distraction of the viral spike protein to its cognate receptor angiotensin-converting enzyme 2 and supporting the over-taxed immunity.

Maintaining higher grain production with less reactive nitrogen losses in China: A meta-analysis study.

Managing reactive nitrogen (Nr) in agricultural production is crucial for addressing the triple challenges of food security, climate change and environmental degradation. Intensive work has been conducted to investigate the effects of mitigation strategies on reducing Nr losses by ammonia emission (Nr-NH3), nitrous oxide emission (Nr-N2O) and nitrate leaching (Nr-NO3-) separately. This meta-analysis evaluated the efficiency of each strategy in mitigating Nr losses coupled with grain yield responses. The results indicate that producing one Megagram (Mg) of wheat grains caused higher Nr losses, twice that of rice and 17% that of maize. The Nr-NH3 and Nr-NO3- were the dominant sources of Nr losses of the three crops (96%), while Nr-NH3 only presented 86% of the total Nr losses for rice. Reducing the N rate strategy decreased the yield by 33% and the Nr losses by 62% compared with the conventional rate (150-250 kg N ha-1) as an average of the three crops. In contrast, increasing the N rate higher than 250 kg N ha-1 amplified the yield by 15% but also caused a 71% increase in Nr losses compared with the conventional rate. Although subsurface application decreased Nr losses by 5%, this study rejected this approach as an effective strategy due to a 4% yield decline on average of the grain crops. Slow-release fertilizers decreased Nr-NH3 and Nr-N2O losses by 41-58% and 54-89%, respectively, of the highest losses under urea in the three crops, but also led to yield reductions. Organic amendments achieved the highest drop in Nr-NO3- loss by 66% in maize coupled with yield declines. Biochar increased wheat and maize yields by 0.3 and 0.1 Mg, respectively, coupled with 1 kg reduction in Nr losses. On average, inhibitors augmented the grain yields by 0.2 Mg ha-1 for each 1 kg decline in Nr losses. In conclusion, for sustainable agricultural intensification, biochar (for wheat only) and inhibitors (for the three crops) are strongly recommended as mitigation strategies for Nr losses from grain crop production systems in China.

Discovery of the anticancer drug vinblastine from the endophytic Alternaria alternata and yield improvement by gamma irradiation mutagenesis.

AIMS: Several fungal endophytes were isolated from some medicinal plants and screened for their ability to produce the anticancer drug vinblastine. METHODS AND RESULTS: An isolate was found to produce vinblastine (205·38 µg l-1 ), and the identity of the fungal vinblastine was confirmed by UV spectroscopic, high-performance liquid chromatography and electrospray ionization mass spectrometry analyses. Based on both morphological and molecular studies, the vinblastine-producing strain was identified as Alternaria alternata. Cytotoxic activities of the fungal vinblastine were evaluated against CHO-K1, MCF-7 and HepG-2 cell lines by the MTT assay. The proliferation of these cell lines was inhibited after treatment with fungal vinblastine and the recorded IC50 values of the respective cell lines were 12·15, 8·55 and 7·48 µg ml-1 . A strain improvement programme for improving vinblastine productivity by the fungal strain was also used. In addition, 10 broth media were evaluated for further increasing the production of vinblastine. The yield of vinblastine was intensified by 3·98-fold following gamma irradiation at 1000 Gy, and a stable mutant strain was isolated. Among the screened media, M1D broth (pH 6·0) stimulated the highest vinblastine production of 1553·62 µg l-1 by the isolated mutant strain. CONCLUSIONS: The present study is the first report on the production and yield improvement of the anticancer drug vinblastine by A. alternata. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest A. alternata as a viable and potent source with excellent biotechnological potential for the production of vinblastine.

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum: isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation.

AIMS: Different endophytic fungi were isolated and screened for their digoxin-producing ability. Strain improvement and different culture conditions were studied for more effective production of digoxin. METHODS AND RESULTS: Among the isolated fungi, an isolate produced digoxin in a concentration of 2·07 mg l-1 . The digoxin-producing fungal isolate was identified as Epicoccum nigrum Link according to the morphological features and phylogenetic analyses. The potentiality of the fungal strain for production enhancement of digoxin was performed by gamma radiation mutagenesis. Gamma irradiation dose of 1000 Gy intensified the digoxin yield by five-fold. Using this dose, a stable mutant strain with improved digoxin productivity was isolated and the stability for digoxin production was followed up across four successive generations. In the effort to increase digoxin magnitude, selection of the proper cultivation medium, addition of some elicitors to the most proper medium and several physical fermentation conditions were tested. Fermentation process carried out in malt extract autolysate medium (pH 6·5) supplemented by methyl jasmonate and inoculated with 2 ml of 6-day-old culture and incubated at 25°C for 10 days stimulated the highest production of digoxin to attain 50·14 mg l-1 . Moreover, cytotoxicity of digoxin separated from the fungal culture was tested against five different cancer cell lines. Based on the MTT assay, digoxin inhibited the proliferation of the five different cancer cell lines and the recorded 50% inhibitory concentration ranged from 10·76 to 35·14 µg ml-1 . CONCLUSIONS: This is the first report on the production and enhancement of digoxin using fungal fermentation as a new and alternate source with high productivity. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer new and alternate sources with excellent biotechnological potential for digoxin production by fungal fermentation. Moreover, digoxin proved to be a promising anticancer agent whose anticancer potential should be assessed in prospective cancer therapy.

Agro-industrial wastes for production of paclitaxel by irradiated Aspergillus fumigatus under solid-state fermentation.

AIMS: Paclitaxel is the most profitable drug ever developed in cancer chemotherapy; however, the yield of paclitaxel from microbial platforms is still far from the commercial purpose. Thus, this study was conducted to explore the possibility of solid-state fermentation (SSF) for production of paclitaxel by fungal fermentation. METHODS AND RESULTS: Different agro-industrial wastes were screened as solid substrates for production of paclitaxel by the endophytic Aspergillus fumigatus TXD105 under SSF. Sugarcane bagasse followed by wheat bran, and rice bran were the most suitable substrates for maximum production of paclitaxel. In the effort to increase the paclitaxel production, selection of the most proper moistening agent that supports the production of paclitaxel by the fungal strain was investigated. The effect of varying inoculum concentrations on the production of paclitaxel was also studied. Moreover, optimization of SSF conditions (moisture level, substrate concentrations and nutrients concentration) was adopted using response surface methodology. SSF carried out under the optimum conditions of 20 g sugarcane bagasse, twofold nutrients concentration of the MM1D broth, 80% moisture level and inoculum concentration of 107 spores per ml intensified the paclitaxel concentration to 145·61 mg kg-1 which represents a 10-fold increase. The production of paclitaxel by the fungal strain was further improved via exposure to UV and gamma radiation at specific doses. The paclitaxel concentrations were intensified following UV and gamma radiation to 209·91 and 351·82 mg kg-1 . CONCLUSIONS: This is the first report on the production of paclitaxel using agro-industrial wastes as cheap source that may contribute in lowering the cost of producing paclitaxel. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings offer new and alternate sources with excellent biotechnological potential for paclitaxel production by fungal fermentation.

Biosynthesis of zinc oxide nanoparticles with antimicrobial, anticancer, antioxidant and photocatalytic activities by the endophytic Alternaria tenuissima.

AIMS: Zinc oxide nanoparticles (ZnONPs) were successfully synthesized using the culture filtrate of the endophytic fungus Alternaria tenuissima as a rapid, eco-friendly and cost-effective method. METHODS AND RESULTS: The rapid synthesis of ZnONPs was completed after 20 min as confirmed by UV-Vis spectroscopy. The synthesized ZnONPs showed a single-phase crystalline structure. Dynamic light scattering analysis showed that the synthesized ZnONPs were monodispersed and the recorded polydispersity index value was 0·311. Zeta potential value of -23·92 mV indicated the high stability of ZnONPs. Transmission electron microscope revealed the spherical shape and the mean particle size was 15.45 nm. Functional groups present in the prepared samples of ZnONPs were confirmed by Fourier transform infrared spectroscopy. Additionally, the biological activities of in vitro antimicrobial, anticancer, antioxidant as well as the photocatalytic activities were evaluated. ZnONPs showed broad spectrum of antimicrobial potential against all the tested plant and human pathogens. Based on the MTT assay, ZnONPs inhibited the proliferation of normal human melanocytes, human breast and liver cancer cell lines with IC50 concentrations of 55·76, 18·02 and 16·87 µg ml-1 . ZnONPs exhibited promising antioxidant potential with 50% inhibitory concentration of 102·13 µg ml-1 . Moreover, ZnONPs showed efficient degradation of methylene blue dye. CONCLUSIONS: The synthesized ZnONPs showed promising activities that can be better explored in the near future for many medical, agricultural and industrial applications. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests a new and alternate approach with the excellent biotechnological potentiality for the production of ZnONPs which could open up the way for the industrial manufacture of nanoparticles using microbial platforms.

The rational design, synthesis, and antimicrobial investigation of 2-Amino-4-Methylthiazole analogues inhibitors of GlcN-6-P synthase.

A series of novel 2-Amino-4-Methylthiazole analogs were developed via three-step reaction encompassing hydrazine-1-carboximidamide motif to combat Gram-positive and Gram-negative bacterial and fungal infections. Noticeably, the thiazole-carboximidamide derivatives 4a-d displayed excellent antimicrobial activity and the most efficacious analogue 4d with MIC/MBC values of 0.5 and 4 µg/mL, compared to reference drugs with very low toxicity to mammalian cells, resulting in a prominent selectivity more than 100 folds. Microscopic investigation of 4d biphenyl analogue showed cell wall lysis and promote rapid bactericidal activity though disrupting the bacterial membrane. In addition, an interesting in vitro investigation against GlcN-6-P Synthase Inhibition was done which showed potency in the nanomolar range. Meanwhile, this is the first study deploying a biomimicking strategy to design potent thiazole-carboximidamides that targeting GlcN-6-P Synthase as antimicrobial agents. Importantly, Molecular modeling simulation was done for the most active 4d analogue to study the interaction of this analogue which showed good binding propensity to glucosamine binding site which support the in vitro data.

Groundwater vulnerability and trace element dispersion in the Quaternary aquifers along middle Upper Egypt.

Association of trace metal concentrations in water is problematic; however, its information is scarce and sometimes contradicted. This work presents variations in dissolved major constituents and trace element concentrations along the quaternary aquifers located in middle Upper Egypt (Minia and Assiut governorates). A total of 205 groundwater samples from these aquifers were collected. Auxiliary parameters (pH, alkalinity, and conductivity), major cations (Ca2+, Mg2+, Na+, and K+), dominant anions (HCO3-, SO42-, Cl-, and NO3-), and trace element (B, Fe, Cu, Mn, Ni, Pb, Cd, and Cr) concentrations were measured in all samples. Univariate (correlation coefficient and scatter matrix) analysis was employed combined with multivariate (principal coordinates analysis) analysis to identify the chemical characteristics of groundwater that are responsible for generating most of the variability within the dataset. Also, hierarchical cluster analysis was applied to classify the geochemical origin of the groundwater constituents. The results indicate that the groundwater pollution is mainly due to water-rock interactions, including aquifer matrix dissolution, redox reaction of trace metals, input from wastewater, and agricultural fertilizers.

Biotechnological applications of quorum sensing inhibition as novel therapeutic strategies for multidrug resistant pathogens.

High incidence of antibiotic resistance among bacterial clinical isolates necessitates the discovery of new targets for inhibition of microbial pathogenicity, without stimulation of microbial resistance. This could be achieved by targeting virulence determinants, which cause host damage and disease. Many pathogenic bacteria elaborate signaling molecules for cellular communication. This signaling system is named quorum sensing system (QS), and it is contingent on the bacterial population density and mediated by signal molecules called pheromones or autoinducers (AIs). Bacteria utilize QS to regulate activities and behaviors including competence, conjugation, symbiosis, virulence, motility, sporulation, antibiotic production, and biofilm formation. Hence, targeting bacterial communicating signals and suppression of QS exhibit a fundamental approach for competing microbial communication. In this review, we illustrate the common up to date approaches to utilize QS circuits in pathogenic bacteria, including Vibrio fischeri, Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii, as novel therapeutic targets.

Antibacterial, antibiofilm and molecular modeling study of some antitumor thiazole based chalcones as a new class of DHFR inhibitors.

Some synthesized antitumor derivatives of thiazole based chalcones including thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues were subjected to be tested against standard microbial strains. Compound 18 showed higher activity against both Gram-positive and Gram-negative bacteria with MIC of 1.0, 1.0, 2.0, 2.0 and 4.0 µg/ml against S. aureus, B. subtilis, M. luteus, E. coli and P. aeuroginosa respectively which is better than ampicillin and very relative to ciprofloxacin standards. Moreover, this compound shows a good anti-biofilm activity against the Gram positive bacteria. Molecular docking studies of synthesized compounds against DHFR enzyme were carried out. Interestingly, active anticancer candidates 22,38, 40 and 41 in addition to most active antimicrobial agents 15, 18 and 20 bind to DHFR with nearly the same amino acid residues as MTX especially mentioning Arg28, Arg70, Asn64 and Lys68 which support our hypothesis that these compounds could act as antitumor or antibacterial via DHFR inhibition. Flexible alignment and surface mapping techniques have further provided lipophilic distributions supporting effective binding to DHFR. ADMET calculations for compounds 15, 18 and 20 suggested that they could be good orally absorbed antibacterial agents while compound 38 could be an orally absorbed anticancer agent with diminished toxicity. The results highlight studied thiazole based chalcones as efficient leads for designing new future antibacterial drug candidates.

Synthesis, antimicrobial, anti-biofilm evaluation, and molecular modelling study of new chalcone linked amines derivatives.

A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques 1H NMR, 13C NMR, and ESI-MS. They were screened for in vitro antibacterial activity. Compounds 36, 37, 38, 42, and 44 are the most active among the synthesised series exhibiting MIC value of 2.0-10.0 µg/ml against different bacterial strains. Compound 36 was equipotent to the standard drug Ampicillin displaying MBC value of 2.0 µg/ml against the bacterial strain Staphylococcus aureus. The products were screened for anti-biofilm activity. Compounds 36, 37, and 38 exhibited promising anti-biofilm activity with IC50 value ranges from 2.4 to 8.6 µg. Molecular modelling was performed suggesting parameters of signalling anti-biofilm mechanism. AspB327 HisB340 (arene-arene interaction) and IleB328 amino acid residues seemed of higher importance to inhibit c-di-GMP. Hydrophobicity may be crucial for activity. ADME calculations suggested that compounds 36, 37, and 38 could be used as good orally absorbed anti-biofilm agents.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors.

2-(1-{4-[(4-Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was exploited as a starting material for the synthesis of two novel series of 5-arylazo-2-hydrazonothiazoles 6a - 6j and 2-hydrazono[1,3,4]thiadiazoles 10a - 10d, incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.

Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration.

Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150-250 µm) or a large pore size (LPC; 250-350 µm). CPX-IMs surface pore size was confirmed by scanning electron microscope. The hardness of NPC, LPC, and SPC CPX-IMs were 58 ± 2.8, 53 ± 1.9, and 50 ± 2.1 N, respectively. The measured porosity values were 41.2 ± 1.53, 65.2 ± 1.1, and 60.7 ± 1.2%, respectively. Differential scanning calorimetry was employed to study the compatibility of ingredients, the effect of injection molding on polymer properties, and implants degradation. Coating of CPX-IMs prolonged drug release to reach a value of 90% release in 40 days. Antibacterial activity tests showed sufficiency of CPX to inhibit pathogens known to cause osteomyelitis. The in vivo study showed tissue compatibilities of the inserted matrices in tested rats with no sign of infection throughout the experiment period. SPC and LPC CPX-IMs demonstrated a better osteointegration, cell adhesion, and infiltration of different types of bone cells within implants structure compared to the non-porous matrix. Furthermore, LPC CPX-IMs showed a superior bone cell attachment and osteointegration relative to SPC CPX-IMs. Findings of this study confirmed the impact of porosity and pore sizes on cell proliferation and fracture healing concurrently with the sustained local antibiotic therapy for treatment or prevention of osteomyelitis.

Mobility and Fate of Pollutants in the Aquifer System of the Northwestern Suez Gulf, Egypt.

The northwestern part of Suez Gulf region is a strategic area in Egypt. It includes important sources of national income. To achieve the development goals, the government has established huge projects in this area (e.g. establishment and expanding of a large commercial port at Ain Sokhna, many industrial zones as well as tourism projects). The utilization of the Suez Gulf resources and their continuing development mainly depend on the creation of actual pollution control programs. The environmental quality control and pollution reduction activities are important ingredients of any economic development program. These different activities in this area depend mainly on the groundwater that is pumped intensively from different water bearing formations or aquifers. The main objective of the present work is compiling the previous studies from the 1980s up to 2015. These studies are concerned with estimating the concentrations of different pollutants in various ecosystems in the northwestern Suez Gulf region. Also, to provide an explanation for the movement of different pollutants such as organic and heavy metals from contaminated land to ground and surface (Gulf) waters. This issue has not been extensively surveyed before, and this review, gives specific directions for future monitoring and remediation strategies in this region.

Synthesis, biological evaluation and molecular modeling study of some new methoxylated 2-benzylthio-quinazoline-4(3H)-ones as nonclassical antifolates.

A new series of 2,3,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 28 and 61 proved to be active DHFR inhibitors with IC50 0.02 and 0.01µM, respectively. Molecular modeling studies concluded that recognition with the key amino acid Phe34 is essential for binding and hence DHFR inhibition. Compounds 34, 56 and 66 showed broad spectrum antimicrobial activity comparable to Gentamicin and Ciprofloxacin. Compounds 40 and 64 showed broad spectrum antitumor activity toward several tumor cell lines and proved to be 10 fold more active than 5-FU, with GI50 MG-MID values of 2.2 and 2.4µM, respectively.

Thymol and carvacrol prevent cisplatin-induced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats.

The aim of the present study is to assess the possible protective effects of thymol and carvacrol against cisplatin (CP)-induced nephrotoxicity. A single dose of CP {6 mg/kg, intraperitoneally (i.p.)} injected to male rats revealed significant increases in serum urea, creatinine, and tumor necrosis factor alpha levels. It also increased kidney contents of malondialdehyde and caspase-3 activity with significant reduction in serum albumin, kidney content of reduced glutathione as well as catalase, and superoxide dismutase activity as compared to that of the control group. In contrast, administration of thymol {20 mg/kg, orally (p.o.)} and/or carvacrol (15 mg/kg, p.o.) for 14 days before CP injection and for 7 days after CP administration restored the kidney function and examined oxidative stress parameters. In conclusion, thymol was more effective nephroprotective than carvacrol. Moreover, a combination of thymol and carvacrol had a synergistic nephroprotective effect that might be attributed to antioxidant, anti-inflammatory, and antiapoptotic activities.

Immobilization technique for enhanced production of the immunosuppressant mycophenolic acid by ultraviolet and gamma-irradiated Penicillium roqueforti.

AIMS: Different entrapment matrices were screened to immobilize two strains of Penicillium roqueforti (AG101 and LG109) for more effective production of mycophenolic acid (MPA). Further improvement in the MPA productivity from immobilization of spores and mycelia was adopted by UV and gamma irradiation. METHODS AND RESULTS: Penicillium roqueforti strains were immobilized in different entrapping carriers and used for MPA production in shake flask cultures. Maximum MPA production was achieved on using an alginate concentration of 3·0% (w/v) and a mycelial fresh weight of 10% (w/v). MPA produced by alginate-immobilized spores and mycelia was almost double in comparison to the free system. The MPA-producing ability of immobilized AG101 and LG109 strain was significantly enhanced by mutagenesis through irradiation by UV (254 nm) for 120 and 90 min, respectively and gamma rays at 0·75 KGy. The feasibility of MPA production in a semi-continuous form by immobilized cells as affected by irradiation was adopted. CONCLUSIONS: MPA production by immobilized spores and mycelia was more intensified by UV and gamma irradiation. Moreover, the immobilized cell culture was superior to free-cell culture. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings indicate the future possibility to reduce the cost of producing fermentation-based drugs.

Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors.

A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34, and 39 proved to be the most active DHFR inhibitors with IC50 values range of 0.1-0.6 µM. Compounds 28, 31 and 33 showed remarkable broad-spectrum antimicrobial activity comparable to the known antibiotic Gentamicin. Compounds 26, 33, 39, 43, 44, 50, 55 and 63 showed broad spectrum antitumor activity with GI values range of 10.1-100%. Molecular modeling study concluded that recognition with key amino acid Glu30, Phe31 and Phe34 is essential for binding. ADMET properties prediction of the active compounds suggested that compounds 29 and 34 could be orally absorbed with diminished toxicity.

GC estimation of organic hydrocarbons that threaten shallow Quaternary sandy aquifer Northwestern Gulf of Suez, Egypt.

Soil and groundwater contamination is one of the important environmental problems at petroleum-related sites, which causes critical environmental and health defects. Severe petroleum hydrocarbon contamination from coastal refinery plant was detected in a shallow Quaternary sandy aquifer is bordered by Gulf in the Northwestern Gulf of Suez, Egypt. The overall objective of this investigation is to estimate the organic hydrocarbons in shallow sandy aquifers, released from continuous major point-source of pollution over a long period of time (91 years ago). This oil refinery contamination resulted mainly in the improper disposal of hydrocarbons and produced water releases caused by equipment failures, vandalism, and accidents that caused direct groundwater pollution or discharge into the gulf. In order to determine the fate of hydrocarbons, detailed field investigations were made to provide intensive deep profile information. Eight composite randomly sediment samples from a test plot were selected for demonstration. The tested plot was 50 m long × 50 m wide × 70 cm deep. Sediment samples were collected using an American auger around the point 29° 57' 33″ N and 32° 30' 40″ E in 2012 and covered an area of 2,500 m(2) which represents nearly 1/15 of total plant area (the total area of the plant is approximately 3.250 km(2)). The detected total petroleum hydrocarbons (TPHs) were 2.44, 2.62, 4.54, 4.78, 2.83, 3.22, 2.56, and 3.13 wt%, respectively. TPH was calculated by differences in weight and subjected to gas chromatography (GC). Hydrocarbons were analyzed on Hewlett-Packard (HP-7890 plus) gas chromatograph equipped with a flame ionization detector (FID). The percentage of paraffine of the investigated TPH samples was 7.33, 7.24, 7.58, 8.25, 10.25, 9.89, 14.77, and 17.53 wt%, respectively.