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Background: Identification of molecules having dual capabilities to reduce postprandial hyperglycemia and oxidative stress is one of the therapeutic approaches to treat diabetes mellitus. In this connection, a library of benzofuran-linked chalcone derivatives were evaluated for their dual action. Methods: A series of substituted benzofuran-linked chalcones (2–33) were synthesized and tested for α-amylase inhibitory as well as 2,2-diphenylpicrylhydrazyl (DPPH) and 2,2′-azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities. Results: All compounds showed α-amylase inhibitory activity ranging from IC50 = 12.81 ± 0.03 to 87.17 ± 0.15 μM, compared with the standard acarbose (IC50 = 13.98 ± 0.03 μM). Compounds also demonstrated radical scavenging potential against DPPH and ABTS radicals. Conclusion: The identified compounds may serve as potential leads for further advanced research.

OBJECTIVES: To determine patient satisfaction in terms of various services such as ease of getting care, in-patient admission, waiting for check-up, staff interaction, medical care, cost of care, and cleanliness in a Tertiary Care Government Hospital. METHODOLOGY: The study design was cross sectional observational. A total of 200 patients meeting our inclusion criteria were enrolled through convenient sampling techniques in this research study. A well-designed questionnaire was used for data collection of admitted patients. RESULTS: Out of 200 patients, 96 (48%) male and 104 (47%) female patients were interviewed. 72% were satisfied with clinical care services, 14% had mixed views while 14% patients were not satisfied at all. CONCLUSION: Patients in general showed their satisfaction in some of the aspects, however, keeping in view the burden a public sector hospital absorbs on a daily basis, and it was imperative to receive unsatisfactory feedback from patients in most of the aspects. Thus, the results of my study recommend to the health care leaders to take practical steps to bring further improvement by developing a proper mechanism for the uplift of public sector hospitals.

Currently the discovery and development of potent

Background: Diabetes mellitus is one of the most chronic metabolic disorders. Since past few years, our research group had synthesized and evaluated libraries of heterocyclic compounds against α and β-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and β-glucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Methods: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques, including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and β-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against α- glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β- glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 μM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

Benzimidazole scaffolds are known to have a diverse range of biological activities and found to be antidiabetic and antioxidant. In this study, a variety of arylated benzimidazoles 1–31 were synthesized. Except for compounds 1, 6, 7, and 8, all are new derivatives. All compounds were screened for α-amylase inhibitory, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. In vitro screening results revealed that all molecules demonstrated significant α-amylase inhibition with IC50 values of 1.86 ± 0.08 to 3.16 ± 0.31 μM as compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). However, compounds showed significant ABTS and DPPH radical scavenging potentials with IC50 values in the range of 1.37 ± 0.21 to 4.00 ± 0.10 μM for ABTS and 1.36 ± 0.09 to 3.60 ± 0.20 μM for DPPH radical scavenging activities when compared to ascorbic acid with IC50 values of 0.72 ± 0.21 and 0.73 ± 0.05 μM for ABTS and DPPH radical scavenging potentials, respectively. Structure–activity relationship (SAR) was established after critical analysis of varying substitution effects on α-amylase inhibitory and radical scavenging (ABTS and DPPH) potentials. However, molecular docking was also performed to figure out the active participation of different groups of synthetic molecules during binding with the active pocket of the α-amylase enzyme.

Aryl hydrazones bearing thiazolyl coumarin hybrids 1–32 were prepared by following 'one-pot' two-steps reaction scheme. Various arylaldehydes were reacted to thiosemicarbazide under acidic condition to form aryl thiosemicarbazone intermediates which in turn treated with 3-bromoacetyl coumarin under basic condition to afford thiazolyl coumarin hybrids 1–32. All hybrids were recognized by EI- and HREI-MS and 1H- and 13C-NMR spectroscopic techniques. Compounds 1–32 were screened for in vitro inhibitory activity against urease enzyme and displayed good to moderate inhibitory potential in the ranges of IC50 = 16.29 ± 1.1–256.30 ± 1.4 µM. Worth stating that compound 21 (IC50 = 16.29 ± 1.1 µM) was identified as more potent urease inhibitor than the standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Derivatives 19 (IC50 = 77.67 ± 1.5 µM) and 30 (IC50 = 71.21 ± 1.6 µM) were found to be moderately active. Structure–activity relationship revealed that -F, -Cl, -OH, and -OMe groups and their respective positions on aryl ring are playing important role in urease enzyme inhibition. Molecular docking studies identified important interaction between the ligand (active hybrids) and urease active site.

N-Aryl-3,4-dihydroisoquinoline carbothioamide analogues 1-22 were synthesized by a simple one-step reaction protocol and subjected to in vitro urease inhibition studies for the first time. All compounds 1-22 were found active and showed significant to moderate urease inhibitory potential. Specifically, analogues 1, 2, 4, and 7 were identified to be more potent (IC50 = 11.2 ± 0.81-20.4 ± 0.22 μM) than the standard thiourea (IC50 = 21.7 ± 0.34 μM). The structure-activity relationship showed that compounds bearing electron-donating groups showed superior activity. Molecular docking study on the most active derivatives revealed a good protein-ligand interaction profile against the corresponding target with key interactions, including hydrogen bonding, hydrophobic, and π-anion interactions.

Purpose of the study: The study aimed to discover the learning strategies of distance learners and their relationship with their intrinsic and extrinsic motivation. Methodology: The study followed a quantitative correlational research design. The study sample comprised 550 female and male students enrolled as distance learners at the university level. The tool of learning strategies MSLQ was adopted from Pintrich et al. (1991) and the scale of intrinsic and extrinsic motivation was adopted from Lepper et al. (2005). The data were analyzed through descriptive and inferential statistical techniques. Main Findings: The findings of the inquiry concluded that the learning strategies of distance learners were directly associated with both intrinsic and extrinsic motivations. Applications of this study: This study is applicable to assess the intrinsic and extrinsic motivation of distance learners enrolled at the university level. Moreover, this study is helpful to understand the relationship between the motivation of learners and their learning styles. Novelty/Originality of this study: Much of the research work has been done in the mainstream education sector, but there is a shortage of empirical data on the relationship between the learning styles of distance learners and their motivation. Thus, this research could be a torchbearer in this area.

Purpose of the study: This research study explores the relationship between life satisfaction, self-esteem, and academic performance of university students. Methodology: A quantitative approach was used to explore the relationship among life satisfaction, self-esteem, and academic performance of university students. In this study, a survey method was employed to collect quantitative data on life satisfaction, self-esteem, and academic performance from 575 students studying in three different public universities of Punjab (Pakistan). A self-esteem scale as a survey instrument initially developed by Rosenberg (1965) and a life satisfaction scale developed by Gilligan and Huebner (2002) were used to collect data. A third scale was developed by the researchers to measure the students’ academic performance. The assembled data were statistically examined using descriptive statistics and Pearson correlation by using SPSS 20th Version. Results: Findings of the study reveal that the level of life satisfaction among university students is comparatively higher than the presence of self-esteem and academic performance. Findings of the study show significant positive associations of university students’ academic performance with their life satisfaction and self-esteem. Applications of this study: This study helps strengthen the factors that promote university students’ academic performance. Novelty/Originality of this study: The novelty of this study is to explore the relationship among life satisfaction, self-esteem, and academic performance of university students for strengthening different dimensions of life satisfaction and self-esteem which ultimately promote university students’ academic performance.

Purpose of the study: This research study aims to measure the entrepreneurial attitude of female university students and investigates the factors contributing to the development of entrepreneurial attitude among female students in Pakistan. The core objective of the study was to develop entrepreneurial attitudes among females and make them capable to adopt small-scale businesses. Methodology: A quantitative approach was employed to measure the entrepreneurial attitude of female students and further exploring different factors affecting the attitude of female students towards adopting the business as a career option. In this study, a survey method was used in which quantitative data on female students’ entrepreneurial attitude and different affecting factors were collected from 2576 female students from eight public sector universities located in Punjab province. The entrepreneurial attitude scale was used as a survey instrument originally developed by Ali, Topping, and Tariq (2011) and further modified by the researchers to measure the entrepreneurial attitude of female students. A factor-based scale was developed to measure the effect of these factors on female students’ entrepreneurial attitudes. The collected data were analyzed using descriptive statistics, Pearson correlation, and regression techniques by using SPSS 16th Version. Results: Findings of multiple regression analysis exhibits that the role of education is the best contributor to the female students’ entrepreneurial attitude. The other contributing factors are family support, technological assistance, business environment, and social support but their contribution is small whereas government initiatives and legal provisions were not supportive for developing entrepreneurial attitudes among female students. Applications of this study: This study can be useful for arranging entrepreneurial career development programs for the development of the entrepreneurial attitude among female students and make them capable to start their entrepreneurial endeavours. Novelty/Originality of this study: The novelty of this study was to investigate the effects of different familial, social, educational, political, environmental, and legal factors on female students’ entrepreneurial attitudes.

Youth enters universities to engage in reasonable occupations in the future. Different organizations demand employees who have high emotional intelligence (EI) as well as good organizational citizenship behavior (OCB). Universities struggle to nurture these skills among the students . The present study explored the association between students' EI and their OCB . The study was descriptive and 650 students from two universities of Punjab were selected as a sample through simple random sampling. A questionnaire-based on two self-reporting scales was developed as a survey instrument to measure students' EI and OCB . The collected data were examined employing descriptive statistics and Pearson correlation. Results demonstrated that university students possessed a high level of EI and OCB. Moreover, students' EI was directly correlated with their OCB. The study exhibits that expressions of emotions intelligently together with the expressions of OCB eventually enhance students' academic performance that is subsequently improving the performance of the universities.

Purpose: The purpose of this study was to examine the perceptions of female university students about their social and educational careers and factors that may promote or hinder their efforts to achieve their targets. Method: Mixed method research design was followed to achieve the research objectives. Three thousand female university students were selected following a multiphase sampling technique to participate in the close-ended questionnaire that was used to collect the quantitative data in the first phase of data collection. Forty female students were randomly selected from the already selected pool of students in the second phase of data collection. An interview schedule was used to collect qualitative data from these 40 students. The qualitative data were analyzed with the help of NVivo following a thematic analysis approach Main Findings: The results showed that the female university students are ready to move forward in their education and contribute effectively in the social spheres of life. Various educational, social, academic, and financial factors that hinder achieving their goals are also identified. Applications of the Study: The results help to make educational activities more systematic, modern, and target-oriented. Novelty/Originality of the Study: The activity contributes to identifying solutions to problems that are associated with the female students’ empowerment and engagement in social and economic activities.

A variety of dihydroquinazolin-4(1H)-one derivatives (1–37) were synthesized via “one-pot” three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02—88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12—89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure–activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.

Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0 µM). Compound 13 (IC50 = 85.0 ± 0.5 µM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme.

Indole-3-acetamides (1–24) were synthesized via coupling of indole-3-acetic acid with various substituted anilines in the presence of coupling reagent 1,1-carbonyldiimidazole. The structures of synthetic molecules were elucidated through different spectroscopic techniques including electron ionization-mass spectroscopy (EI-MS), 1H-, 13C NMR, and high-resolution EI-MS (HREI-MS). These compounds were screened for their antihyperglycemic and antioxidant potentials. All compounds displayed good to moderate inhibition against α-amylase enzyme with IC50 values ranging between 1.09 ± 0.11 and 2.84 ± 0.1 μM compared to the standard acarbose (IC50 = 0.92 ± 0.4 μM). Compound 15 (IC50 = 1.09 ± 0.11 μM) was the most active compound of the series and exhibited good inhibition against α-amylase; in addition, this compound also exhibited good antioxidant potential with IC50 values of 0.35 ± 0.1 and 0.81 ± 0.25 μM in 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, respectively. The binding interactions of synthetic molecules with the enzyme’s active site were confirmed via in silico studies. The current study had identified a number of lead molecules as potential antihyperglycemic and antioxidant agents.

Background: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. Methods: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Results: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring “R” played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Conclusion: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

Scaffold varied dihydropyrimidone derivatives 1–20 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (Ki values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 1–20 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic.

In recent years, blended learning (BL) has grown to occupy an important space in Chinese educational practice. Policymakers have developed many application strategies and platforms and are continuing to develop BL for future use. In order to apply BL in practice, key stakeholders have been using different learning management systems (LMSs), digital platforms, games, hybrid courses, and various forms of social media to create a framework for BL. This study asserts that many visible opportunities have emerged in Chinese higher education through the applications of BL. The advantages of BL are that it fosters stronger academic achievement, student engagement, and cognitive engagement and understanding as well as flexible and quick communication skills, faster interaction skills, technical skills, and adaptability to ever-changing educational practices. On the other hand, BL has brought about some pedagogical and technical difficulties for both learners and practitioners. This study found that most BL courses are not as effective as they could be because they do not have a strong pedagogical framework. Moreover, BL suffers from the technical incompetence of teachers and students, the inefficiency of LMSs, and the unavailability of required resources, such as certain devices and the Internet. Some higher education institutions have become pioneers in Chinese educational practice and been able to successfully adopt BL frameworks and integrate Moodle as well as other platforms and techniques. However, many other institutions’ attempts to adopt BL approaches have not been as effective. In order to better understand how and in what ways BL is being integrated into the educational system, this study overviews the current situation and discusses the strengths and weaknesses of BL in Chinese higher education.

Women’s empowerment is a concept describing the promotion of women doing things independently and in their own interests, being more conducive to their future and physical and mental development; this includes participation in different outdoor activities, including sports. This qualitative study presents data collected from 18 young female students at sports and physical education universities in Southern Punjab (SP) in Pakistan, selected using a snowball sampling technique. The current study explores their gendered and lived experiences of playing sports and engaging in physical activities in patriarchal systems by emphasizing the concept of women’s empowerment in the context of feminism in sports theory. The findings suggest that the participants faced typical gender stereotypes in their families and communities, which position sports and physical activities as being not feminine. The chances for women to participate in sports and physical activities decrease as they grow up. However, the participants used a range of strategies to advance their interests and academic careers in sports and physical activities by resisting and incorporating dominant discourses of women’s participation in sports and physical activities, which also has implications in the internal and external policy domains at the local and national levels. The participants displayed great resilience and optimism, empowering them to enter the male-dominated domains, and thus we labeled them as change agents.

Generalized trust is the most common and natural concept. It plays an important role in society. It depends on the performance of public institutions. Generalized trust in public institutions creates a positive environment in society. The major purpose of the current study was to analyze the generalized trust of university students in public institutions. 600 students were randomly selected as a sample from four public universities of Punjab. The questionnaire was used to collect the data. The questionnaire demonstrated Cronbach Alpha Coefficients of more than .70. Findings revealed that generalized trust of students was higher on the military institution, but overall, students showed distrust in these institutions such as police, parliament. Results also showed that fighting terrorism, corruption, political pressure, poverty, lack of education are major problems faced by public institutions.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin, indomethacin, flufenamic acid and phenylbutazone are used to treat most of the inflammatory disorders. These NSAIDs are also associated with serious side effects including gastric ulceration, nephrotoxicity, and bleeding, mainly due to acidic nature. Hence, there is a need to identify highly potent and safer treatment for inflammatory disorders. Methods: Herein, synthetic hydrazinyl thiazole substituted coumarins and chromones 1-48 were evaluated for ROS inhibitory activity. ROS were generated from zymosan activated whole blood phagocytes. Results: Among all tested compounds, compounds 1 (IC50 = 38.3 ± 7.1 μM), 2 (IC50 = 5.7 ± 0.2 μM), 5 (IC50 = 28.3 ± 3.5 μM), 23 (IC50 = 12.5 ± 3.1 μM), 27 (IC50 = 32.8 ± 1.1 μM), 39 (IC50 = 20.2 ± 1.6 μM), and 42 (IC50 = 43.2 ± 3.8 μM) showed potent ROS inhibition as compared to standard ibuprofen (IC50 = 54.3 ± 1.9 μM). Whereas, compounds 3 (IC50 = 134.7 ± 1.0 μM), 16 (IC50 = 75.4 ± 7.2 μM), 24 (IC50 = 102.4 ± 1.0 μM), and 31 (IC50 = 86.6 ± 1.5 μM) were found to be moderately active. Compounds 1, 2, 5, 23, 27, 39, and 42, having potent ROS inhibitory activity were also screened for their nitric oxide (NO) inhibition. Cytotoxicity was also checked for all active compounds on NIH-3T3 cell line. Cyclohexamide (IC50 = 0.13 ± 0.02 μM) was used as standard. Conclusion: Identified active compounds from these libraries may serve as lead candidates for future research in order to obtain a more potent, and safer anti-inflammatory agent.

Novel ibuprofen derivatives 1–19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2–19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1H-, and 13C-NMR spectroscopic techniques. The synthetic molecules 1–19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC50 = 2.96–178 μM as compared to the standard thiourea (IC50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2–4, 6, 7, 9, 11–15, 17, and 18 demonstrated remarkable inhibitory activity with IC50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC50 value of 37.3 ± 0.41 μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.

A convenient and facile CuCl2·2H2O catalyzed one-pot synthetic strategy was designed for the conversion of readily available dimedone into highly functionalized N-arylhydrazinecarbothioamide based indazole derivatives. The product yields were found to be moderate to good without purification requirements. Structural features of the synthetic compounds were confirmed by various spectroscopic techniques such as 1H NMR, 13C NMR, EI-MS, FAB-MS, HREI-MS, and HRFAB-MS. The reaction intermediates were also quenched and characterized. Plausible reaction mechanisms were also discussed. Keywords: One-pot synthesis, Dimedone, Indazole, Carbothioamides

Currently the discovery and development of potent β-glucuronidase inhibitors is an active area of research due to the observation that increased activity of this enzyme is associated with many pathological conditions, such as colon cancer, renal diseases, and infections of the urinary tract. In this study, twenty-seven 2-aminopyrimidine derivatives 1–27 were synthesized by fusion of 2-amino-4,6-dichloropyrimidine with a variety of amines in the presence of triethylamine without using any solvent and catalyst, in good to excellent yields. All synthesized compounds were characterized by EI-MS, HREI-MS and NMR spectroscopy. Compounds 1–27 were then evaluated for their β-glucuronidase inhibitory activity, and among them, compound 24 (IC50 = 2.8 ± 0.10 µM) showed an activity much superior to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 µM). To predict the binding mode of the substrate and β-glucuronidase, in silico study was performed. Conclusively, this study has identified a potent β-glucuronidase inhibitor that deserves to be further studied for the development of pharmaceutical products.

Introduction: Antioxidants are known to prevent oxidative stress-induced damage to the biomolecules and thus, delay the onset of cancers and many age-related diseases. Therefore, the development of novel and potent antioxidants is justified. Method: During this study, we synthesized symmetrical Bis-Schiff bases of carbohydrazide 1-27, and evaluated their in vitro antioxidative activity and cytotoxic activity. Results: Among synthesized compounds, six compounds 20 (IC50 = 12.89 ± 0.02 μM), 16 (IC50 = 14.32 ± 0.43 μM), 17 (IC50 = 18.52 ± 0.83 μM), 19 (IC50 = 22.84 ± 0.62 μM), 24 (IC50 = 35.1 ± 0.82 μM) and 15 (IC50 = 40.03 ± 1.06 μM) showed an excellent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, better than the standard butylatedhydroxyanisole (BHA) (IC50 = 44.6 ± 0.6 μM). Likewise, two compounds 16 (IC50 = 4.3 ± 1.3 μM) and 20 (IC50 = 6.6 ± 1.6 μM) showed oxidative burst scavenging activity better than the standard drug ibuprofen (IC50 = 11.2 ± 1.9 μM). Some synthesized compounds showed good to moderate toxicity against prostate cancer (PC-3) cell lines. Conclusion: This study has identified potent antioxidants and good cytotoxic agents with the potential to further investigate.

This research examines how curriculum delivery predicts entrepreneurial skills, with knowledge of information and communication technology (ICT) as a mediator. Curriculum delivery with the multiple dimensions of objectives, contents, teaching strategies, and feedback and assessment was used in this study, and a quantitative research design was adopted. A questionnaire survey was used to collect data from 482 students at six universities in Lahore, Pakistan, and the partial-least-squares structural equation model in SmartPLS 3.2 was used for data analysis. The results show that all dimensions of curriculum delivery (i) do not influence entrepreneurial skills and (ii) positively influence the knowledge of ICT. Also, in the indirect relationships, all dimensions of curriculum delivery (i.e., objectives, contents, teaching strategies, and feedback and assessment) are associated positively with ICT knowledge. Therefore, ICT knowledge plays a mediating role between curriculum delivery and entrepreneurial skills. The results also show that curriculum delivery for educational entrepreneurs is not working effectively and efficiently in Pakistani universities, and it is concluded that curriculum delivery and ICT knowledge boost entrepreneurial skills. Finally, the conclusions, limitations, and practical implications of this study are presented in detail.

This study investigated the relationships among emotional intelligence (EI), relational engagement (RE), and cognitive outcomes (COs). A survey questionnaire containing 34 statements was completed by 338 undergraduate students from the four universities of China, with responses recorded on a 7-point Likert-type scale. The relationships were examined using the partial least squares structural equation modeling. The findings showed that EI influenced the COs directly and indirectly during the pandemic. In the forms of self-regulation (SR) and social skills (SS), the high levels of EI improved the COs of the students. Further, the aspects of EI, such as SR, self-awareness (SA), empathy (E), motivation (M), and SS were found to improve the RE of the students. The RE was positively correlated with the COs, indicating its potential for improving critical thinking among university students. Finally, the RE was a key mediator of the relationship between the EI and COs. It is concluded that the students with higher levels of EI and RE may achieve better COs. The implications of the research and suggestions for future studies are also discussed.

Sixteen derivatives of dithiin diisoimide 2a-2p have been synthesized and screened for antibacterial and antifungal activity. Compounds 2a-2g and 2i-2p are almost same or more active than gentamicine against Acinetobacter. Whereby compound 2,6-didodecyl

A microwave-assisted diazotization reaction of ciprofloxacin was used for the analysis of ciprofloxacin in pharmaceutical samples. The ciprofloxacin was diazotized with phenol using acidified sodium nitrite in a domestic microwave oven. Faster microwave heating and microwave effects were found to be very effective for the process of diazotization. The microwave-assisted reaction was initiated in an acidic media and the colored product was stabilized in a slightly basic medium using a NaOH solution as a neutralizer. The product was found to exhibit the maximum absorbance at 440 nm. All of the experimental conditions like the concentration of reagents, microwave power and reaction time were optimized. The optimum concentrations for phenol, sodium nitrite, HCl and NaOH were found to be 140 ppm, 300 ppm, 0.006 M and 0.006 M respectively. The optimum reaction time was found to be 2 min and a medium high power of the microwave was found to be most effective. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be 1.08 and 3.61 mg L-1 respectively. The developed method was successfully applied for the determination of ciprofloxacin in pharmaceutical samples. This new spectrophotometric method for the analysis of ciprofloxacin is fast, sensitive, easy and cost effective.

The maximum quantum yield of photosystem II (as reflected by variable to maximum chlorophyll a fluorescence, Fv /Fm ) is regarded as one of the most important photosynthetic parameters. The genetic basis underlying natural variation in Fv /Fm , which shows low level of variations in plants under non-stress conditions, is not easy to be exploited using the conventional gene cloning approaches. Thus, in order to answer this question, we have followed another strategy: we used genome-wide association study (GWAS) and transgenic analysis in a rice mini-core collection. We report here that four single-nucleotide polymorphisms, located in the promoter region of β-glucosidase 5 (BGlu-5), are associated with observed variation in Fv /Fm . Indeed, our transgenic analysis showed a good correlation between BGlu-5 and Fv /Fm . Thus, our work demonstrates the feasibility of using GWAS to study natural variation in Fv /Fm , suggesting that cis-element polymorphism, affecting the BGlu-5 expression level, may, indirectly, contribute to Fv /Fm variation in rice through the gibberellin signaling pathway. Further research is needed to understand the mechanism of our novel observation.

This study deals with the synthesis of benzophenone sulfonamides hybrids (1–31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-nitrobenzenesulfonohydrazide), 2 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-3′′-nitrobenzenesulfonohydrazide), 3 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-methoxybenzenesulfonohydrazide), 4 (3′′,5′′-dichloro-2′′-hydroxy-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2′′,4′′-dichloro-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)-N′-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2′′-chloro-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC50 value in the range of 3.90–17.99 µM. These compounds showed superior activity than standard acetohydroxamic acid (IC50 = 29.20 ± 1.01 µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by 1H NMR, 13C NMR, EI-MS and FAB-MS spectroscopic techniques.

Background:Barbituric acid derivatives are a versatile group of compounds which are identified as potential pharmacophores for the treatment of anxiety, epilepsy and other psychiatric disorders. They are also used as anesthetics and have sound effects on the motor and sensory functions. Barbiturates are malonylurea derivatives with a variety of substituents at C-5 position showing resemblance with nitrogen and sulfur containing compounds like thiouracil which exhibited potent anticancer and antiviral activities. Recently, barbituric acid derivatives have also received great interest for applications in nanoscience.Objective:Synthesis of 5-arylidene-N,N-diethylthiobarbiturates, biological evaluation as potential α-glucosidase inhibitors and molecular modeling.Methods:In the present study, N,N-Diethylthiobarbituric acid derivatives were synthesized by refluxing of N,N-diethylthiobarbituric acid and different aromatic aldehydes in distilled water. In a typical reaction; a mixture of N,N-diethylthiobarbituric acid 0.20 g (1 mmol) and 5-bromo-2- hydroxybenzaldehyde 0.199 g (1 mmol) mixed in 10 mL distilled water and reflux for 30 minutes. After completion of the reaction, the corresponding product 1 was filtered and dried and yield calculated. It was crystallized from ethanol. The structures of synthesized compounds 1-25 were carried out by using 1H, 13C NMR, EI spectroscopy and CHN analysis used for the determination of their structures. The α-glucosidase inhibition assay was performed as given by Chapdelaine et al., with slight modifications and optimization.Results:Our newly synthesized compounds showed a varying degree of α-glucosidase inhibition and at least four of them were found as potent inhibitors. Compounds 6, 5, 17, 11 exhibited IC50 values (Mean±SEM) of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively, as compared to standard acarbose (IC50, 38.25 ± 0.12 µM).Conclusion:Our present study has shown that compounds 6, 5, 17, 11 exhibited IC50 values of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively. The studies were supported by in silico data analysis.

Background:Inflammation is a biological rejoinder of vascular tissues against destructive agents e.g. irritants, damaged cell or pathogens. During inflammation, respiratory burst occurs by activated phagocytes which help to destroy invading pathogens. Phagocytic cells such as neutrophils and macrophages are one of the major sources of reactive oxygen species (ROS) and nitric oxide (NO). Normally, the redox environment is maintained by various antioxidant defense systems, however, these reactive oxygen species may be destructive and can lead to various pathological conditions.Methods:Benzophenone esters and sulfonates (1-18) were synthesized through one pot synthesis by reacting 4-hydroxy benzophenone either different benzoyl chloride or sulfonyl chloride. These synthetic compounds were evaluated for their in vitro immunosuppressive potential on two parameters of innate immune response including inhibition of intracellular reactive oxygen species (ROS) and nitric oxide (NO). ROS were induced in polymorphonuclear leukocytes (PMNs) isolated from human whole blood by serum opsonized zymosan stimulation, whereas NO were produced in J774.2 cells by lipopolysachharides (LPS) stimulation. Moreover, cytotoxicity of compounds was also determined using NIH-3T3 fibroblast cells (ATCC, Manassas, USA) was evaluated by using the standard MTT colorimetric assay.Results:All compounds inhibited the production of ROS at various extent among which compounds 2, 5, 6, 8, 10, 13 and 16 were found to be the potent inhibitors of ROS with IC50 values ranging between (1.0 - 2.2 µg/mL) as compared to ibuprofen (IC50 = 2.5 ± 0.6 µg/mL) as the standard drug. Compounds 2, 7, 11, 13, 14 and 18 showed good inhibition of NO production with % inhibition values ranging between (63.6% - 76.7%) at concentration of 25 µg/mL as compared to NG-monomethyl-Larginine (L-NMMA 65.6 ± 1.1 µg/mL) as the standard. All other derivatives showed moderate to low level of inhibition on both tested parameters. Cytotoxicity activity also showed nontoxicity of synthetic compounds. Structures of all the synthetic compounds were confirmed through 1H-NMR, 13C-NMR, EI-MS and HREI-MS spectroscopic techniques.Conclusion:Compounds 2 and 13 were found to be good dual antiinflammatory (ROS and NO) agent. However, compounds 5, 6, 8, 10 and 16 were found to be selectively active for ROS inhibitory studies. Compounds 7, 11, 14 and 18 were discriminatory active at NO inhibition assay. These initial findings of antiinflammatory activity concluded that these compounds might have the potential to develop a novel non-steroidal antiinflammatory drugs (NSAIDs), non-acidic antiinflammatory agent. Most active compounds 2, 5-8, 10, 13, 14 and 16 showed nontoxicity of synthetic compounds.

Benzohydrazide derivatives 1–43 were synthesized via “one-pot” reaction and structural characterization of these synthetic derivatives was carried out by different spectroscopic techniques such as 1H NMR and EI-MS. The synthetic molecules were evaluated for their in vitro urease inhibitory activity. All synthetic derivatives showed good inhibitory activities in the range of (IC50 = 0.87 ± 0.31–19.0 ± 0.25 µM) as compared to the standard thiourea (IC50 = 21.25 ± 0.15 µM), except seven compounds 17, 18, 23, 24, 29, 30, and 41 which were found to be inactive. The most active compound of the series was compound 36 (IC50 = 0.87 ± 0.31 μM) having two chloro groups at meta positions of ring A and methoxy group at para position of ring B. The structure–activity relationship (SAR) of the active compounds was established on the basis of different substituents and their positions in the molecules. Kinetic studies of the active compounds revealed that compounds can inhibit enzyme via competitive and noncompetitive modes. In silico study was also performed to understand the binding interactions of the molecules (ligand) with the active site of enzyme.

Background: The role of small molecules as antioxidants to prevent the oxidation of other molecules and inhibit them from radical formation is the area of much interest to cure disease especially cancer. Moreover, the antioxidants play important role as stabilizers to prevent oxidation of fuels and lubricants. Methods: In the present study, fifteen tetrakis-Schiff’s bases derivatives (1-15) were synthesized and screened for their antioxidant activities. Compounds 1-15 were synthesized by continuous stirring of reaction mixture of 1,4-bis (hydrazonomethyl)benzene (1 mmol) with various substituted aromatic aldehydes (2 mmol) in distilled water using acetic acid as catalyst at room temperature for 2-10 min. Results: Our present study showed that all compounds are better ferrous ion-chelating agents except compound 1,4-bis((E)-((E)-(3,4-dimethoxybenzylidene)hydrazono)methyl)benzene (6) (IC50 = 329.26 ± 4.75 µM) which has slightly low activity than the standard EDTA (IC50 = 318.40 ± 5.53 μM). In addition, DPPH radical scavenging activity of eleven compounds showed higher activity than the standard. However, remaining four compounds showed comparable radical scavenging activity to the standard DPPH (IC50 = 257.77 ± 4.60 µM). Conclusion: The series of fifteen Schiff’s bases (1-15) were synthesized and evaluated as antioxidants. From both assays, it has been demonstrated that most of the tetrakis-Schiff’s bases have potential to serve as leads for the development of antioxidant agents for future research.

Background: Alkaline Phosphatase (AP) is a physiologically important metalloenzyme that belongs to a large family of ectonucleotidase enzymes. Over-expression of tissue non-specific alkaline phosphatase has been linked with ectopic calcification including vascular and aortic calcification. In Vascular Smooth Muscles Cells (VSMCs), the high level of Reactive Oxygen Species (ROS) resulted in the up-regulation of TNAP. Accordingly, there is a need to identify highly potent and selective inhibitors of APs for treatment of disorders related to hyper activity of APs. Methods: Herein, a series of coumarinyl alkyl/aryl sulfonates (1-40) with known Reactive Oxygen Species (ROS) inhibition activity, was evaluated for alkaline phosphatase inhibition against human Tissue Non-specific Alkaline Phosphatase (hTNAP) and Intestinal Alkaline Phosphatase (hIAP). Results: With the exception of only two compounds, all other compounds in the series exhibited excellent AP inhibition. For hIAP and hTNAP inhibition, IC50 values were observed in the range 0.62-23.5 µM, and 0.51-21.5 µM, respectively. Levamisole (IC50 = 20.21 ± 1.9 µM) and Lphenylalanine (IC50 = 100.1 ± 3.15 µM) were used as standards for hIAP and hTNAP inhibitory activities, respectively. 4-Substituted coumarinyl sulfonate derivative 23 (IC50 = 0.62 ± 0.02 µM) was found to be the most potent hIAP inhibitor. Another 4-substituted coumarinyl sulfonate derivative 16 (IC50 = 0.51 ± 0.03 µM) was found to be the most active hTNAP inhibitor. Some of the compounds were also found to be highly selective inhibitors of APs. Detailed Structure-Activity Relationship (SAR) and Structure-Selectivity Relationship (SSR) analysis were carried out to identify structural elements necessary for efficient and selective AP inhibition. Molecular modeling and docking studies were carried out to rationalize the most probable binding site interactions of the inhibitors with the AP enzymes. In order to evaluate drug-likeness of compounds, in silico ADMETox evaluation was carried out, most of the compounds were found to have favorable ADME profiles with good predicted oral bioavailability. X-ray crystal structures of compounds 38 and 39 were also determined. Conclusion: Compounds from this series may serve as lead candidates for future research in order to design even more potent, and selective inhibitors of APs.

A precise, accurate and sensitive liquid chromatographic method is presented for the simultaneous analysis of moxifloxacin, levofloxacin, ciprofloxacin and dexamethasone in reference drugs, ophthalmic dosage form and in physiological fluids. Separation was achieved on a C1(8)analytical column with acetonitrile-phosphate buffer (35:65 v/v) as mobile phase which was pumped isocratically at a flow rate of 1.0 mL min-1 and monitored at 254 nm wavelength. The calibration curve was linear in range of 40-10 000 ng mL-1. Test results in pharmaceutical and physiological samples showed excellent drug recovery (96.5-102.3 %) with good precision (0.81-2.3 % RSD). Test results were linear to sample concentration and correlation coefficient was more than 0.9990. The small value of quantification and detection levels showed the method to be sensitive enough for use in clinical and industrial investigations of all the mentioned drugs.

Novel derivatives of flurbiprofen 1–18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2–9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11–15, and benzyl substituted 2-mercapto oxadiazole derivatives 16–18 were synthesized and characterized by EI-MS, 1H and 13C NMR spectroscopic techniques. All derivatives 1–18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC50 = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC50 = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC50 = 1.69 ± 0.1 µM), 3 (IC50 = 1.04 ± 0.3 µM), 9 (IC50 = 1.25 ± 1.05 µM), and 13 (IC50 = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme.

Non-photochemical quenching (NPQ) of the excited state of chlorophyll a is a major photoprotective mechanism plants utilize to survive under high light. Here, we report the impact of long-term light quality treatment on photosynthetic properties, especially NPQ in rice. We used three LED-based light regimes, i.e., red (648–672 nm), blue (438–460 nm), and “warm” white light (529–624 nm), with the incident photon flux density of 300 µmol photons m−2 s−1, the difference in the absorbed photon flux densities by leaves grown under different light quality being less than 7%. Our results show that blue light, as compared to white light, induced a significant decrease in Fv/Fm, a decreased rate of reduction of P700+ after P700 was completely oxidized; furthermore, blue light also induced higher NPQ with an increased initial speed of NPQ induction, which corresponds to the qE component of NPQ, and a lower maximum quantum yield of PSII, i.e., Y(II). In contrast, rice grown under long-term red light showed decreased Y(II) and increased NPQ, but with no change in Fv/Fm. Furthermore, we found that rice grown under either blue or red light showed decreased transcript abundance of both catalase and ascorbate peroxidase, together with an increased H2O2 content, as compared to rice grown under white light. All these data suggest that even under a moderate incident light level, rice grown under blue or red light led to compromised antioxidant system, which contributed to decreased quantum yield of photosystem II and increased NPQ.

BACKGROUND Glucuronidation is essential for the metabolism and excretion of toxic substances. β-Glucuronidase enzyme slows down the process of glucuronidation, and thus plays an important role in the on-set of colorectal carcinoma, and many other diseases. Inhibition of β- glucuronidase activity is thus identified as an important approach for the treatment of several diseases. OBJECTIVE Current study was aimed to synthesize a library of 2-oxo-1,2,3,4-tetrahydropyrimidine and to evaluate their β-glucuronidase inhibitory activity, and their mode of enzyme inhibition. METHOD We synthesized a series of 2-oxo-1,2,3,4-tetrahydropyrimidines 1-25 by fusing urea, ethyl acetoacetate, and a variety of aldehydes using copper nitrate trihydrate as catalyst. All synthesized compounds were evaluated for their in vitro β-glucuronidase inhibitory activity. In addition, molecular docking studies were also performed by using MOE docking tools. RESULTS Eighteen compounds showed inhibitory activity better than the standard D-saccharic acid 1,4-lactone, a well known β-glucuronidase inhibitor (IC50 = 45.75 ± 2.16 µM). Compound 20 (IC50 = 1.36 ± 0.03 µM) showed an excellent inhibitory activity, thirty-five folds superior to the standard. Docking results highlighted the role of various chemical moieties at different positions on 2- oxo-1,2,3,4-tetrahydropyrimidine skeleton in enzyme inhibitory activity. CONCLUSION This study has identified a class of potent β-glucuronidase inhibitors with the potential to be investigated further.

Acarbose and voglibose are well-known α-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1–18 for their potential α-amylase inhibitory activity. Structures of synthetic derivatives 1–18 were identified by different spectroscopic techniques. All compounds 1–18 (IC50 = 1.61 ± 0.16 μM to 2.38 ± 0.09 μM) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). A number of derivatives including 8–12 (IC50 = 1.68 ± 0.1 μM to 1.97 ± 0.07 μM) and 14–16 (IC50 = 1.61 ± 0.16 μM to 1.93 ± 0.07 μM) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α-amylase enzyme.

Background Inflammation is defined as the response of immune system cells to damaged or injured tissues. The major symptoms of inflammation include increased blood flow, cellular influx, edema, elevated cellular metabolism, reactive oxygen species (ROS) nitric oxide (NO) and vasodilation. This normally protective mechanism against harmful agents when this normal mechanism becomes dysregulated that can cause serious illnesses including ulcerative colitis, Crohn's disease, rheumatoid arthritis, osteoarthritis, sepsis, and chronic pulmonary inflammation. Method In this study synthetic transformations on diclofenac were carried out in search of better non-steroidal antiinflammatory drugs (NSAIDs), non-acidic, antiinflammatory agents. For this purpose diclofenac derivatives (2-20) were synthesized from diclofenac (1). All derivatives (2-20) and parent diclofenac (1) were evaluated for their antiinflammatory effect using different parameters including suppression of intracellular reactive oxygen species (ROS), produced by whole blood phagocytes, produced by neutrophils, and inhibition of nitric oxide (NO) production from J774.2 macrophages. The most active compound also evaluated for cytotoxicity activity. Results Diclofenac (1) inhibited the ROS with an IC50 of 3.9 ± 2.8, 1.2 ± 0.0 µg/mL respectively and inhibited NO with an IC50 of 30.01 ± 0.01 µg/mL. Among its derivatives 4, 5, 11, 16, and 20, showed better antiinflammatory potential. The compound 5 was found to be the most potent inhibitor of intracellular ROS as well as NO with IC50 values of 1.9 ± 0.9, 1.7 ± 0.4 µg/mL respectively and 7.13 ± 1.0 µg/mL, respectively, and showed good inhibitory activity than parent diclofenac. The most active compounds were tested for their toxic effect on NIH-3T3 cells where all compounds were found to be non-toxic compared to the standard cytotoxic drug cyclohexamide. Conclusion Five derivatives were found to be active. Compound 5 was found to be the most potent inhibitor of ROS and NO compared to parent diclofenac 1 and standard drugs ibuprofen and L-NMMA, respectively. The most active compounds 1, 4, 5, 11 and 20 were found to be non-toxic on NIH-3T3 cells. Compound 4, 5, and 20 also showed good antiinflammatory potential, compound 11 and 16 showed moderate and low level of inhibition, respectively.

The cytochrome b6f (cyt b6f) acts as a common linker of electron transport between photosystems I and II in oxygenic photosynthesis. PetM, one of eight subunits of the cyt b6f complex, is a small hydrophobic subunit at the outside periphery, the functional mechanism of which remains to be elucidated in higher plants. In this work, we found that unlike the PetM mutant in Synechocystis sp. PCC 6803, the Arabidopsis thaliana PetM mutant showed a bleached phenotype with yellowish leaves, block of photosynthetic electron transport and loss of photo-autotrophy, similar to the Arabidopsis PetC mutant. Although PetM is relatively conserved between higher plants and cyanobacteria, Synechocystis PetM could not rescue the PetM-knockout phenotype in Arabidopsis. We provide evidence that the Synechocystis PetM did not stably bind to the Arabidopsis cyt b6f complex. Based on these results, we suggest that PetM is required by Arabidopsis to maintain the function of the cyt b6f complex, likely through its close link with core subunits to form a tight ‘fence’ that stabilizes the core of the complex.

Diabetes mellitus is one of the most prevalent diseases nowadays. Several marketed drugs are available for the cure and treatment of diabetes, but there is still a dire need of introducing compatible drug molecules with lesser side effects. The current study is based on the synthesis of isatin thiazole derivatives 4-30 via the Hantzsch reaction. The synthetic compounds were characterized using different spectroscopic techniques and evaluated for their α-amylase and α-glucosidase inhibition potential. Of 27 isatin thiazoles, five (4, 5, 10, 12, and 16) displayed good activities against the α-amylase enzyme with IC

The present study comprised of the synthesis of dicyanoaniline derivatives of pyridine, thiophene, furan, and substituted phenyl 1–29. All synthetic derivatives were evaluated for their potential to inhibit α-amylase and α-glucosidase enzymes. The synthesized compounds are classified into three categories A, B, and C based on variable substituents at R1 and R2, and the structure–activity relationship was discussed accordingly. Amongst twenty-nine derivatives, 1–29, five compounds 2, 9, 18, 23, and 24 displayed excellent inhibition against α-amylase and α-glucosidase enzymes with the IC50 values ranging between 20.33 ± 0.02–25.50 ± 0.06 µM and 21.01 ± 0.12–27.75 ± 0.17 µM, respectively, while other compounds showed moderate to weak inhibition against both enzymes. Acarbose was used as the positive control in this study. The enzyme kinetic studies showed non-competitive and un-competitive types of inhibition mechanism against α-amylase and α-glucosidase enzymes, respectively. In silico studies have demonstrated the involvement of these molecules in numerous binding interactions within the active site of the enzyme.