Synthesis and biological evaluation of aminomethyl and alkoxymethyl derivatives as carbonic anhydrase,acetylcholinesterase and butyrylcholinesterase inhibitors

Compounds containing nitrogen and sulfur atoms can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. Therefore, the reactions of aminomethylation and alkoxymethylation of mercaptobenzothiazole, mercaptobenzoxazole and 2-aminothiazole were developed. Additionally, the alkoxymethyl derivatives of mercaptobenzoxazole and 2-aminothiazole were synthesized by a reaction with hemiformals, which are prepared by the reaction of alcohols and formaldehyde. In this study, the inhibitory effects of these molecules were investigated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes and carbonic anhydrase I, and II isoenzymes (hCA I and II). Both hCA isoenzymes were significantly inhibited by the recently synthesized molecules, with K_i values in the range of 58–157?nM for hCA I, and 81–215?nM for hCA II. Additionally, the K_i parameters of these molecules for BChE and AChE were calculated in the ranges 23–88 and 18–78?nM, respectively.     

Design of potent fluoro-substituted chalcones as antimicrobial agents

Owing to ever-increasing bacterial and fungal drug resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9–15, and 20–23) using a structure–activity relationship approach. Target compounds were evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv and antimicrobial activity against five common pathogenic bacterial and three common fungal strains. Three derivatives (3, 9, and 10) displayed significant antitubercular activity with IC₅₀ values of ≤16,760. Compounds derived from trimethoxy substituent scaffolds with monofluoro substitution on the B ring of the chalcone structure exhibited superior inhibition activity compared to corresponding hydroxy analogs. In terms of antimicrobial activity, most compounds (3, 9, 12–14, and 23) exhibited moderate to potent activity against the bacteria, and the antifungal activities of compounds 3, 13, 15, 20, and 22 were comparable to those of reference drugs ampicillin and fluconazole.     

Phycoremediation of municipal wastewater by microalgae to produce biofuel

Municipal wastewater (WW), if not properly remediated, poses a threat to the environment and human health by carrying significant loads of nutrients and pathogens. These contaminants pollute rivers, lakes, and natural reservoirs where they cause eutrophication and pathogen-mediated diseases. However, the high nutrient content of WW makes it an ideal environment for remediation with microalgae that require high nutrient concentrations for growth and are not susceptible to toxins and pathogens. Given that an appropriate algal strain is used for remediation, the incurred biomass can be refined for the production of biofuel. Four microalgal species (Chlamydomonas reinhardtii, Chlorella sp., Parachlorella kessleri-I, and Nannochloropsis gaditana) were screened for efficient phycoremediation of municipal WW and potential use for biodiesel production. Among the four strains tested, P. kessleri-I showed the highest growth rate and biomass production in 100% WW. It efficiently removed all major nutrients with a removal rate of up to 98% for phosphate after 10 days of growth in 100% municipal WW collected from Delhi. The growth of P. kessleri-I in WW resulted in a 50% increase of biomass and a 115% increase of lipid yield in comparison to growth in control media. The Fatty acid methyl ester (FAME), and fuel properties of lipids isolated from cells grown in WW complied with international standards. The present study provides evidence that the green alga P. kessleri-I effectively remediates municipal WW and can be used to produce biodiesel.     

DNA extraction from crayfish exoskeleton

Crayfish exoskeleton (CE) samples are generally less invasive and easy to be collected. However, it is difficult to extract DNA from them. This study was intended to investigate CE as a DNA source and design an easy and efficient DNA extraction protocol for polymerase chain reactions. Specific primer pair (PPO-F, PPO-R) was used to amplify extracted DNA from CE, and compared to crayfish tail muscle DNA sample. Moreover, seven microsatellites markers were used to amplify the CE DNA samples set. Since the extracted DNA from CE is suitable for gene amplification, the results present usefulness of CE as an easy and convenient DNA source for PCR-based population genetic research.     

The effect of synthesis media on the properties of substituted polyaniline/chitosan composites

Substituted polyaniline/chitosan (sPANI/Ch) composites were chemically synthesized in H₂SO₄ and CH₃COOH synthesis media. Structural and physical properties of the composites were characterized by using FTIR, SEM, TGA, UV–vis, XRD techniques, and conductivity measurements. The effect of synthesis media on morphology, thermal stability, conductivity, and crystalline properties was investigated. Chemical interactions between substituted polyanilines and chitosan were explained using FTIR spectra results. The different morphological surfaces were observed in SEM images of the composites. The size of the substituted polyaniline/chitosan (sPANI/Ch) composites was in nanoscale, and the composites synthesized in acetic acid media showed smaller structures than those of H₂SO₄ media and pure chitosan. It was interpreted from XRD results that the composites have amorphous structure and the PNEANI/Ch–CH₃COOH composite has the highest crystallinity.     

Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities

In conditions of overnutrition, cardiac cells must cope with a multitude of extracellular signals generated by changes in nutrient load (glucose, amino acids, and lipids) and the hormonal milieu [increased insulin (INS), ANG II, and adverse cytokine/adipokine profile]. Herein, we review the diverse compensatory/adaptive mechanisms that counter the deleterious effects of excess nutrients and growth factors. We largely focus the discussion on evidence obtained from Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats, which are useful models to evaluate adaptive and maladaptive metabolic, structural, and functional cardiac remodeling. One adaptive mechanism present in the INS-resistant ZO, but absent in the diabetic ZDF heart, involves an interaction between the nutrient sensor kinase mammalian target of rapamycin complex 1 (mTORC1) and ANG II-type 2 receptor (AT2R). Recent evidence supports a cardioprotective role for the AT2R; for example, suppression of AT2R activation interferes with antihypertrophic/antifibrotic effects of AT1R blockade, and AT2R agonism improves cardiac structure and function. We propose a scenario, whereby mTORC1-signaling-mediated increase in AT2R expression in the INS-resistant ZO heart is a cardioprotective adaptation to overnutrition. In contrast to the ZO rat, heart tissues of ZDF rats do not show activation of mTORC1. We posit that such a lack of activation of the mTOR?AT2R integrative pathway in cardiac tissue under conditions of obesity-induced diabetes may be a metabolic switch associated with INS deficiency and clinical diabetes.     

Evaluation of Status of Trace and Toxic Metals in Biological Samples (Scalp Hair, Blood, and Urine) of Normal and Anemic Children of Two Age Groups

Anemia affects a substantial portion of the world’s population, provoking severe health problems as well as important economic losses to the region in which this condition is found. This study was designed to compare the levels of essential trace and toxic elements in scalp hair, blood, and urine samples of anemic children (n = 132) with age range 1–5 and 6–10 years of both genders. For a comparative study, 134 non-anemic age- and sex-matched children as control subjects, residing in the same city, were selected. The metals in the biological samples were measured by flame atomic absorption spectrophotometry/electrothermal atomic absorption spectrometry prior to microwave-assisted acid digestion. The proposed method was validated using certified reference samples of hair, blood, and urine. The results indicated significantly lower levels of iron, copper, and zinc in the biological samples as compared to the control children of both genders (p = 0.01–0.008). The mean values of lead and cadmium were significantly high in all three biological samples of anemic children as compared to non-anemic children of both age groups (p = 0.005–0.001). The ratios of essential metal to toxic metals in the biological samples of anemic children of both age groups were significantly lower than that of controls. Deficiency of essential trace metals and high level of toxic metals may play a role in the development of anemia in the subjects under study.     

Lead (Pb)-Induced Regulation of Growth, Photosynthesis, and Mineral Nutrition in Maize (Zea mays L.) Plants at Early Growth Stages

The phytotoxic effects of lead (Pb) on seed germinability, seedling growth, photosynthetic performance, and nutrient accumulation (K(+) and Cu(2+)) in two maize genotypes (EV-1098 and EV-77) treated with varying levels of PbSO(4) (0.01, 0.1, and 1.0 mg L(-1)) were appraised in this study. In the seed germination experiment, lead stress significantly reduced seed germination percentage and index, plumule and radicle lengths as well as fresh and dry weights in both genotypes. In the second experiment, lengths and fresh and dry weights of shoots and roots decreased due to Pb in both genotypes with increase in plant age. Higher Pb levels also decreased photosynthetic rate (A), water use efficiency (A/E), and intrinsic water use efficiency (A/g(s)), but increased transpiration rate (E) and C(i)/C(a) ratio as a result of increase in stomatal conductance (g(s)). The concentrations of K(+) and Cu(2+) decreased in root, stem, and leaves of both genotypes, which could be a direct consequence of multifold increase in Pb concentration in these tissues. Overall, cv. EV-1098 had better Pb tolerance potential than EV-77 because the former genotype showed less reduction in seed germinability parameters, photosynthetic performance, and K(+) and Cu(2+) accumulation in shoot and root under lead stress.     

Chromium and Manganese Levels in Biological Samples of Pakistani Myocardial Infarction Patients at Different Stages as Related to Controls

It has been speculated that trace elements may play a role in the pathogenesis of heart diseases In the present study, we aimed to access the levels of chromium (Cr) and manganese (Mn) in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both gender age ranged (45?C60?years) at first, second, and third heart attack (n?=?130), hospitalized in cardiac ward of National Hospital of Hyderabad city (Pakistan). For comparison, healthy age-matched referent subjects (n?=?61), of both gender were also selected. The Cr and Mn in biological samples were measured by electrothermal atomic absorption spectrometry, prior to microwave-assisted acid digestion. The validity of the methodology was checked by the biological certified reference materials. During this study, 78% of 32 registered patients of third MI attack (aged >50?years) were died. In these subjects the concentration of Cr and Mn were decreased by 24.7% and 19.8% in scalp hair, while in blood samples 17.9% and 12.4%, respectively, as compared to those who tolerated third MI attack (p?=?0.063). Although these data do not prove a causal relationship, these results are consistent with the hypothesis that heart disease may cause deficiencies of certain essential trace elements. The excretion levels of Cr and Mn in urine samples of first MCI were higher than controls at p values (0.029 and 0.011), respectively, whereas the excretion rates of both elements were further enhance after second myocardial infarction attack. The Cr and Mn concentration was inversely associated with the risk of myocardial infarction attacks in both genders. These results add to an increasing body of evidence that, Cr and Mn are importance for cardiovascular health.     

Evaluation of Essential Trace and Toxic Elements in Biological Samples of Normal and Night Blindness Children of Age Groups 3–7 and 8–12 Years

The most common cause of blindness in developing countries is vitamin A deficiency. The World Health Organization estimates 13.8 million children to have some degree of visual loss related to vitamin A deficiency. The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence biological samples composition. Vitamin and mineral deficiency prevents more than two billion people from achieving their full intellectual and physical potential. This study was designed to compare the levels of Zn, Mg, Ca, K, Na, As, Cd, and Pb in scalp hair, blood, and urine of night blindness children age ranged 3–7 and 8–12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of As, Ca, Cd, K, Pb, Mg, Na, and Zn in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The results of this study showed that the mean values of As, Cd, Na, and Pb were significantly higher in scalp hair, blood, and urine samples of male and female night blindness children than in referents (p?<?0.001), whereas the concentrations of Zn, Ca, K, and Mg were lower in the scalp hair and blood but higher in the urine samples of night blindness children. These data present guidance to clinicians and other professional investigating deficiency of essential mineral elements in biological samples (scalp hair and blood) of night blindness children.