Displaying publications 1 - 20 of 38 in total

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  1. Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice
    Khalid K, Lim HX, Anwar A, Tan SH, Hwang JS, Ong SK, et al.
    AAPS PharmSciTech, 2024 Mar 12;25(3):60.
    PMID: 38472523 DOI: 10.1208/s12249-024-02778-x
    The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.
  2. Fulltext Indole-3-acetamides: As Potential Antihyperglycemic and Antioxidant Agents; Synthesis, In Vitro α-Amylase Inhibitory Activity, Structure-Activity Relationship, and In Silico Studies
    Kanwal, Khan KM, Chigurupati S, Ali F, Younus M, Aldubayan M, et al.
    ACS Omega, 2021 Jan 26;6(3):2264-2275.
    PMID: 33521466 DOI: 10.1021/acsomega.0c05581
    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.
  3. Fulltext The development of DNA vaccines against SARS-CoV-2
    Khalid K, Poh CL
    Adv Med Sci, 2023 Sep;68(2):213-226.
    PMID: 37364379 DOI: 10.1016/j.advms.2023.05.003
    BACKGROUND: The COVID-19 pandemic exerted significant impacts on public health and global economy. Research efforts to develop vaccines at warp speed against SARS-CoV-2 led to novel mRNA, viral vectored, and inactivated vaccines being administered. The current COVID-19 vaccines incorporate the full S protein of the SARS-CoV-2 Wuhan strain but rapidly emerging variants of concern (VOCs) have led to significant reductions in protective efficacies. There is an urgent need to develop next-generation vaccines which could effectively prevent COVID-19.

    METHODS: PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2023.

    RESULTS: A promising solution to the problem of emerging variants is a DNA vaccine platform since it can be easily modified. Besides expressing whole protein antigens, DNA vaccines can also be constructed to include specific nucleotide genes encoding highly conserved and immunogenic epitopes from the S protein as well as from other structural/non-structural proteins to develop effective vaccines against VOCs. DNA vaccines are associated with low transfection efficiencies which could be enhanced by chemical, genetic, and molecular adjuvants as well as delivery systems.

    CONCLUSIONS: The DNA vaccine platform offers a promising solution to the design of effective vaccines. The challenge of limited immunogenicity in humans might be solved through the use of genetic modifications such as the addition of nuclear localization signal (NLS) peptide gene, strong promoters, MARs, introns, TLR agonists, CD40L, and the development of appropriate delivery systems utilizing nanoparticles to increase uptake by APCs in enhancing the induction of potent immune responses.

  4. Odds of HIV among incarcerated drug users: a systematic review and meta-analysis of Asian countries
    Hussain HU, Kumar KA, Rehan ST, Khan Z, Hashmi MR, Khabir Y, et al.
    Ann Med Surg (Lond), 2023 Nov;85(11):5584-5592.
    PMID: 37915701 DOI: 10.1097/MS9.0000000000001242
    BACKGROUND: HIV makes up a large portion of infectious diseases globally. People injecting drugs in prisons are at high risk for contracting HIV infection. Prisons house ~10.2 million people globally, making them a high-risk setting for HIV transmission. This systematic review summarizes the available data on the odds of developing HIV infection among imprisoned people who inject drugs (PWIDs) in Asian regions.

    METHODS: The authors electronically assessed published studies from January, 2000 to December, 2022, including studies that investigated the odds of HIV in imprisoned PWIDs. We extensively searched PubMed, ERIC, and Cochrane Central and Google Scholar with no constraints in language or time. All the observational studies evaluating the chances of HIV in Asian prisoners with an exposure group of PWIDs and a control group of non-injecting-drug users were included in our analysis.

    RESULTS: The databases search yielded 254 potential studies, 10 observational studies of which having a total of 17 333 participants were included. A low or moderate risk of bias was reported in all the studies except one case-control. The pooled analysis showed a significant association between PWIDs and the chances of contracting HIV infection (Odds ratio=6.40; 95% CI=3.89-10.52; P<0.00001; I2=53%).

    CONCLUSION: This study found a vital correlation between injecting-drug usage during imprisonment and HIV transmission speed. The results of this meta-analysis support the need to prevent HIV and conducting treatment programs in high-risk settings like prisons.

  5. Fulltext Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae
    Anwar A, Mungroo MR, Khan S, Fatima I, Rafique R, Kanwal, et al.
    Antibiotics (Basel), 2020 Apr 17;9(4).
    PMID: 32316387 DOI: 10.3390/antibiotics9040188
    Balamuthia mandrillaris and Naegleriafowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.
  6. Fulltext Isoniazid Conjugated Magnetic Nanoparticles Loaded with Amphotericin B as a Potent Antiamoebic Agent against Acanthamoeba castellanii
    Iqbal K, Abdalla SAO, Anwar A, Iqbal KM, Shah MR, Anwar A, et al.
    Antibiotics (Basel), 2020 May 25;9(5).
    PMID: 32466210 DOI: 10.3390/antibiotics9050276
    The pathogenic free-living amoeba, Acanthamoeba castellanii, is responsible for a rare but deadly central nervous system infection, granulomatous amoebic encephalitis and a blinding eye disease called Acanthamoeba keratitis. Currently, a combination of biguanides, amidine, azoles and antibiotics are used to manage these infections; however, the host cell cytotoxicity of these drugs remains a challenge. Furthermore, Acanthamoeba species are capable of transforming to the cyst form to resist chemotherapy. Herein, we have developed a nano drug delivery system based on iron oxide nanoparticles conjugated with isoniazid, which were further loaded with amphotericin B (ISO-NPs-AMP) to cause potent antiamoebic effects against Acanthamoeba castellanii. The IC50 of isoniazid conjugated with magnetic nanoparticles and loaded with amphotericin B was found to be 45 μg/mL against Acanthamoeba castellanii trophozoites and 50 μg/mL against cysts. The results obtained in this study have promising implications in drug discovery as these nanomaterials exhibited high trophicidal and cysticidal effects, as well as limited cytotoxicity against rat and human cells.
  7. Fulltext Are pharmacists on the front lines of the opioid epidemic? A cross-sectional study of the practices and competencies of community and hospital pharmacists in Punjab, Pakistan
    Mubarak N, Zahid T, Rana FR, Ijaz UE, Shabbir A, Manzoor M, et al.
    BMJ Open, 2023 Nov 21;13(11):e079507.
    PMID: 37989383 DOI: 10.1136/bmjopen-2023-079507
    INTRODUCTION: Countries are grappling with a rapidly worsening upsurge in the opioid-related overdose deaths, misuse and abuse. There is a dearth of data in Pakistan regarding the practices and competencies of pharmacists in handling opioid-related issues.

    STUDY DESIGN: A cross-sectional study, conducted across Punjab, Pakistan.

    METHOD: The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists.

    RESULTS: 504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents 'never' or 'sometimes' made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p<0.05). In competency evaluation, three priority areas emerged that require additional training, that is, 'opioid overdose management', 'opioid use monitoring' and 'therapeutic uses of opioids'.

    CONCLUSION: Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce.

  8. Indole acrylonitriles as potential anti-hyperglycemic agents: Synthesis, α-glucosidase inhibitory activity and molecular docking studies
    Solangi M, Kanwal, Mohammed Khan K, Saleem F, Hameed S, Iqbal J, et al.
    Bioorg Med Chem, 2020 Nov 01;28(21):115605.
    PMID: 33065441 DOI: 10.1016/j.bmc.2020.115605
    One of the most prevailing metabolic disorder diabetes mellitus has become the global health issue that has to be addressed and cured. Different marketed drugs have been made available for the treatment of diabetes but there is still a need of introducing new therapeutic agents that are economical and have lesser or no side effects. The current study deals with the synthesis of indole acrylonitriles (3-23) and the evaluation of these compounds for their potential for α-glucosidase inhibition. The structures of these synthetic molecules were deduced by using different spectroscopic techniques. Acarbose (IC50 = 2.91 ± 0.02 μM) was used as standard in this study and the synthetic molecules (3-23) have shown promising α-glucosidase inhibitory activity. Compounds 4, 8, 10, 11, 14, 18, and 21 displayed superior inhibition of α-glucosidase enzyme in the range of (IC50 = 0.53 ± 0.01-1.36 ± 0.04 μM) as compared to the standard acarbose. Compound 10 (IC50 = 0.53 ± 0.01 μM) was the most effective inhibitor of this library and displayed many folds enhanced activity in contrast to the standard. Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. This study had identified a number of potential α-glucosidase inhibitors that can be used for further research to identify a potent therapeutic agent against diabetes.
  9. Syntheses, in vitro α-amylase and α-glucosidase dual inhibitory activities of 4-amino-1,2,4-triazole derivatives their molecular docking and kinetic studies
    Yeye EO, Kanwal, Mohammed Khan K, Chigurupati S, Wadood A, Ur Rehman A, et al.
    Bioorg Med Chem, 2020 06 01;28(11):115467.
    PMID: 32327353 DOI: 10.1016/j.bmc.2020.115467
    Thirty-three 4-amino-1,2,4-triazole derivatives 1-33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via1H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1-33 exhibited good to moderate in vitro α-amylase and α-glucosidase inhibitory activities in the range of IC50 values 2.01 ± 0.03-6.44 ± 0.16 and 2.09 ± 0.08-6.54 ± 0.10 µM as compared to the standard acarbose (IC50 = 1.92 ± 0.17 µM) and (IC50 = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1-33 followed mixed and non-competitive type of inhibitions against α-amylase and α-glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies.
  10. Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies
    Tajudeen Bale A, Mohammed Khan K, Salar U, Chigurupati S, Fasina T, Ali F, et al.
    Bioorg Chem, 2018 09;79:179-189.
    PMID: 29763804 DOI: 10.1016/j.bioorg.2018.05.003
    Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1-13 and bis-chalcones 14-18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50 = 1.25 ± 1.05-2.40 ± 0.09 µM as compared to the standard acarbose (IC50 = 1.04 ± 0.3 µM). Limited structure-activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.
  11. Synthesis of new indazole based dual inhibitors of α-glucosidase and α-amylase enzymes, their in vitro, in silico and kinetics studies
    Rafique R, Khan KM, Arshia, Kanwal, Chigurupati S, Wadood A, et al.
    Bioorg Chem, 2020 01;94:103195.
    PMID: 31451297 DOI: 10.1016/j.bioorg.2019.103195
    The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition.
  12. Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies
    Saleem F, Kanwal, Khan KM, Chigurupati S, Solangi M, Nemala AR, et al.
    Bioorg Chem, 2021 01;106:104489.
    PMID: 33272713 DOI: 10.1016/j.bioorg.2020.104489
    Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.
  13. Polymer-modified mesoporous silica microcubes (P@MSMCs) for the synergistic oxidative entrapment of Ag(i), Ti(iv), and Zn(ii) from natural river water
    Jahan S, Salman M, Alias YB, Abu Bakar AFB, Mansoor F, Kanwal S
    Dalton Trans, 2020 Jun 23;49(24):8265-8273.
    PMID: 32463410 DOI: 10.1039/d0dt01274b
    Herein, we demonstrate a hydrothermal route to the one-pot synthesis of polymeric mesoporous silica microcubes (P@MSMCs) for the adsorption of heavy metal ions. During the synthesis of P@MSMCs from column silica gel, the roles and combination of the polymer and an etchant were characterized. Moreover, the porosity of P@MSMCs was tailored by adjusting the reaction temperature between 75 °C and 200 °C. The characterization through UV, FTIR, FESEM, XRD, BET, and EDX techniques exhibited that P@MSMCs have a well-ordered mesoporous structure with cubic morphology. The P@MSMCs had a diameter of 2 μm, with an average pore volume and pore size of 0.69 cm3 g-1 and 10.08 nm, respectively. The results indicated that the P@MSMCs have excellent adsorption capacity for Ag(i), Ti(iv), and Zn(ii) due to the formation of an aggregated complex. These aggregations led to affordable density difference-based separation of these metal ions through centrifugation, filtration or simple decantation. The removal efficiencies for Ag(i), Ti(iv), and Zn(ii) were observed to be 520, 720, and 850 mg g-1, respectively. The kinetic studies demonstrated that the adsorption performance fitted well to the pseudo-second-order kinetic model. The as-synthesized P@MSMCs were stable in the wide pH range of 4-8. Significantly, the recycling or reuse results displayed effective adsorption performance of these P@MSMCs for up to 5 cycles. The adsorption results obtained herein will promote the development of similar strategies for the removal of heavy metal ions from natural water.
  14. Nexus between corporate social responsibility and financial and non-financial sectors' performance: a non-linear and disaggregated approach
    Shabbir MS, Aslam E, Irshad A, Bilal K, Aziz S, Abbasi BA, et al.
    Environ Sci Pollut Res Int, 2020 Nov;27(31):39164-39179.
    PMID: 32642899 DOI: 10.1007/s11356-020-09972-x
    The objective of this study is to examine the relationship between corporate social performance (CSP) as proxy of corporate social responsibility (CSR) and corporate firm's performance (CFP) in the context of Pakistani financial and non-financial firms sectors. This study comprises two main firm's performance indicators such as market base (excess stock returns) and accounting base (returns on assets and returns on capital). The data set starts from 2011 to 2017 and consists of three hundred and fifty (350) firms on equal numbers of financial and non-financial firms. This study uses a non-linear and disaggregated approach for data analysis. The results of the linear model indicate that CSP and returns on capital have a negative relationship, while the non-linear model of CSP and accounting base performance as CFP have positive association in the domain of long run. There is a significant relationship that exist among environmental social governance (ESG) disclosure score, government sub-components score, and social performance. However, a U-shaped association found between CFP and government sub-components, which further suggest that governance has a vital role toward CSP and CFP components.
  15. Recent advances in the application of silica nanostructures for highly improved water treatment: a review
    Salman M, Jahan S, Kanwal S, Mansoor F
    Environ Sci Pollut Res Int, 2019 Jul;26(21):21065-21084.
    PMID: 31124071 DOI: 10.1007/s11356-019-05428-z
    The demand for high-quality safe and clean water supply has revolutionized water treatment technologies and become a most focused subject of environmental science. Water contamination generally marks the presence of numerous toxic and harmful substances. These contaminants such as heavy metals, organic and inorganic pollutants, oil wastes, and chemical dyes are discharged from various industrial effluents and domestic wastes. Among several water treatment technologies, the utilization of silica nanostructures has received considerable attention due to their stability, sustainability, and cost-effective properties. As such, this review outlines the latest innovative approaches for synthesis and application of silica nanostructures in water treatment, apart from exploring the gaps that limit their large-scale industrial application. In addition, future challenges for improved water remediation and water quality technologies are keenly discussed.
  16. Modeling the significance of green orientation and culture on green innovation performance: moderating effect of firm size and green implementation
    Bhatti SM, Al Mamun A, Wu M, Naznen F, Kanwal S, Makhbul ZKM
    Environ Sci Pollut Res Int, 2023 Sep;30(44):99855-99874.
    PMID: 37615918 DOI: 10.1007/s11356-023-29353-4
    The current global trend in sustainable business practices is to optimize green innovation performance. To protect the environment and maintain their own survival, organizations must strengthen their green innovation capabilities. Drawing on the recourse-based view and ecology modernization theory (EMT), this study examines the direct effect of green strategic orientations, green entrepreneurial orientation, green market orientation, green innovation orientation, and green organizational culture on the firm's green innovation capability, as well as the mediating effect of green innovation capability on the relationship of these four factors and green innovation performance. Besides, this study also explored the moderating effects of green management system implementation and firm size on the association between green innovation capability and green innovation performance. To test the hypothesized model, a questionnaire survey was administered to gather responses from 293 medium-sized and large manufacturing firms operating in Pakistan. The partial least squares method was used for data analysis. The results revealed that green entrepreneurial orientation, green market orientation, green innovation orientation, and green organizational culture positively impacted green innovation capability, which subsequently positively influenced green innovation performance. Moreover, effective implementation of green management systems can bolster the effect of green innovation capability on green innovation performance, and the mediating effect of green innovation capability has also been confirmed. These indicated that the management of medium and large manufacturing firms operating in Pakistan should focus on encouraging green innovation and training employees regarding the latest eco-friendly technologies to attain performance and sustainable development goals. Policymakers should implement green business development programs and offer rewards or penalties for promoting compliance. The present study contributes greatly to the literature by applying EMT as an alternative to address the mediating role of green innovation capability and the moderating effect of green management system implementation in enhancing firms' green innovation performance.
  17. Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies
    Hameed S, Kanwal, Seraj F, Rafique R, Chigurupati S, Wadood A, et al.
    Eur J Med Chem, 2019 Dec 01;183:111677.
    PMID: 31514061 DOI: 10.1016/j.ejmech.2019.111677
    Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ± 1.31 μM), (IC50 = 2.5 ± 1.21 μM), 36 (IC50 = 2.12 ± 1.35 μM), (IC50 = 2.21 ± 1.08 μM), and 37 (IC50 = 2.00 ± 1.22 μM), (IC50 = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.
  18. Novel antiacanthamoebic compounds belonging to quinazolinones
    Anwar A, Shahbaz MS, Saad SM, Kanwal, Khan KM, Siddiqui R, et al.
    Eur J Med Chem, 2019 Nov 15;182:111575.
    PMID: 31415900 DOI: 10.1016/j.ejmech.2019.111575
    We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2, 5, 8, and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii-mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii.
  19. Synthesis, in vitro β-glucuronidase inhibitory potential and molecular docking studies of quinolines
    Bano B, Arshia, Khan KM, Kanwal, Fatima B, Taha M, et al.
    Eur J Med Chem, 2017 Oct 20;139:849-864.
    PMID: 28865280 DOI: 10.1016/j.ejmech.2017.08.052
    In this study synthesis and β-glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline (1-40) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β-glucuronidase. Nonetheless, compounds 1, 2, 5, 13, and 22-24 having IC50 values in the range of 1.60-8.40 μM showed superior activity than the standard saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Moreover, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites. Structures of all the synthetic compounds were confirmed through (1)H NMR, EI-MS and HREI-MS spectroscopic techniques.
  20. 2-Aryl benzimidazoles: Synthesis, In vitro α-amylase inhibitory activity, and molecular docking study
    Adegboye AA, Khan KM, Salar U, Aboaba SA, Kanwal, Chigurupati S, et al.
    Eur J Med Chem, 2018 Apr 25;150:248-260.
    PMID: 29533872 DOI: 10.1016/j.ejmech.2018.03.011
    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC50 = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted.
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