Displaying publications 1 - 20 of 38 in total

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  1. Ranjha MMAN, Kanwal R, Shafique B, Arshad RN, Irfan S, Kieliszek M, et al.
    Molecules, 2021 Aug 12;26(16).
    PMID: 34443475 DOI: 10.3390/molecules26164893
    Different parts of a plant (seeds, fruits, flower, leaves, stem, and roots) contain numerous biologically active compounds called "phytoconstituents" that consist of phenolics, minerals, amino acids, and vitamins. The conventional techniques applied to extract these phytoconstituents have several drawbacks including poor performance, low yields, more solvent use, long processing time, and thermally degrading by-products. In contrast, modern and advanced extraction nonthermal technologies such as pulsed electric field (PEF) assist in easier and efficient identification, characterization, and analysis of bioactive ingredients. Other advantages of PEF include cost-efficacy, less time, and solvent consumption with improved yields. This review covers the applications of PEF to obtain bioactive components, essential oils, proteins, pectin, and other important materials from various parts of the plant. Numerous studies compiled in the current evaluation concluded PEF as the best solution to extract phytoconstituents used in the food and pharmaceutical industries. PEF-assisted extraction leads to a higher yield, utilizes less solvents and energy, and it saves a lot of time compared to traditional extraction methods. PEF extraction design should be safe and efficient enough to prevent the degradation of phytoconstituents and oils.
  2. 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.
  3. Abutayyem H, Alam MK, Kanwal B, Alswairki HJ, Alogaibi YA
    J Orthod Sci, 2023;12:51.
    PMID: 37881658 DOI: 10.4103/jos.jos_53_23
    Infection control is essential to protect both the doctor and the patient by preventing the spread of infectious diseases. There is no exception in the field of dentistry, particularly in orthodontics, where numerous appliances are used for a variety of functions and also because the mouth cavity has the highest concentration of bacteria of any body part. Through this systematic review, we aimed to assess the various methods of sterilization employed in an orthodontic setting. Using relevant keywords, reference searches, and citation searches, the databases such as PubMed, MEDLINE, Web of Science, Cochrane, and Scopus were all searched; a total of 206 documents were found, of which 113 were initially selected. The remaining 23 distinct papers were initially made available after 90 publications that were identical to or similar to one another were eliminated. The final selection was made from eight documents that met all inclusion and exclusion requirements. The existing methods of sterilization were found to be competent in dealing with the microorganisms found in a typical orthodontic setting. The chemical method of sterilization was the norm in most of the studies that we assessed, with glutaraldehyde and peracetic acid (PAA) being the most commonly employed compounds for disinfection. PROSPERO Registration Number: CRD42022380831.
  4. Abutayyem H, Alam MK, Kanwal B, Alswairki HJ, Alogaibi YA
    J Orthod Sci, 2023;12:50.
    PMID: 37881657 DOI: 10.4103/jos.jos_52_23
    A variety of metals and alloys are employed in the field of orthodontics, primary of which happen to be the construction of wires. Through this systematic review, we aimed to assess the various metallurgical characteristics of the said metals and alloys. Four hundred and eighty-two documents in total were found after a thorough search of the online journals, and 169 of the papers were initially chosen. Ultimately, 16 documents were selected that satisfied the necessary inclusion and exclusion criteria, primarily in vitro studies, literature reviews, and comparative analyses. NiTi alloy was found to be the most commonly used alloy in construction of orthodontic wires across all the studies that we had selected for our review. It also had better performance and consistency in terms of its usage as depicted by the meta-analysis performed, with stainless steel wires being a close second primarily due to its lesser cost compared to the former. Metallurgy and orthodontics are inextricably linked with one another. The various components of orthodontics such as wires, pliers, and other instruments utilize the metallurgical characteristics of metals and alloys that are specially prepared for the challenges of this field. PROSPERO Registration Number: CRD42022378444.
  5. Mustafa ZU, Manzoor MN, Shahid A, Salman M, Hayat K, Yasmin K, et al.
    J Multidiscip Healthc, 2022;15:2553-2562.
    PMID: 36388630 DOI: 10.2147/JMDH.S376664
    Purpose: Antimicrobial resistance (AMR) is leading to greater therapeutic cost, length of hospital stays, adverse events, morbidity and mortality. Hospital-based antimicrobial stewardship programs (ASPs) engaging physicians, pharmacists, microbiologists and nurses are considered as effective way to ensure appropriate use of antimicrobial agents. The aims of our study were to assess nurses' perception, involvement, confidence and barriers towards hospital-based ASPs, and use the findings to provide future guidance.

    Methods: A web-based, cross-sectional study was conducted among the nurses serving at eleven hospitals of Punjab province of Pakistan during a period of two months (December 2021-January 2022). Data were collected using a validated self-administered questionnaire. All data were analyzed using SPSS version 22.

    Results: A total of 583 nurses participated in the study (response rate = 77.7%). All the participants were female staff nurses and 86% had a minimum of 3 years of working experience. The overall median score on the perception towards ASPs among the nurses was 18 (IQR: 16, 19) on a 0 to 20 scale whereas median score on the involvement in ASPs was 18 (IQR: 15, 37) on a 0 to 64 scale. Median perception and involvement score were statistically significantly differed by age (p < 0.001) and years of experience (p < 0.001). The overall median score on the confidence to perform ASP activities was 22 (IQR: 14, 24) on a 0 to 28 scale. Lack of knowledge, insufficient support from administration, and heavy workload were found to be the common barriers to perform ASP.

    Conclusion: Our study concluded that Pakistani nurses have positive perception but limited involvement in ASPs. Moreover, they are confident to perform ASP besides many barriers.

  6. Rizwan M, Selvanathan V, Rasool A, Qureshi MAUR, Iqbal DN, Kanwal Q, et al.
    Water Air Soil Pollut, 2022;233(12):493.
    PMID: 36466935 DOI: 10.1007/s11270-022-05904-2
    The production of synthetic drugs is considered a huge milestone in the healthcare sector, transforming the overall health, aging, and lifestyle of the general population. Due to the surge in production and consumption, pharmaceutical drugs have emerged as potential environmental pollutants that are toxic with low biodegradability. Traditional chromatographic techniques in practice are time-consuming and expensive, despite good precision. Alternatively, electroanalytical techniques are recently identified to be selective, rapid, sensitive, and easier for drug detection. Metal-organic frameworks (MOFs) are known for their intrinsic porous nature, high surface area, and diversity in structural design that provides credible drug-sensing capacities. Long-term reusability and maintaining chemo-structural integrity are major challenges that are countered by ligand-metal combinations, optimization of synthetic conditions, functionalization, and direct MOFs growth over the electrode surface. Moreover, chemical instability and lower conductivities limited the mass commercialization of MOF-based materials in the fields of biosensing, imaging, drug release, therapeutics, and clinical diagnostics. This review is dedicated to analyzing the various combinations of MOFs used for electrochemical detection of pharmaceutical drugs, comprising antibiotics, analgesics, anticancer, antituberculosis, and veterinary drugs. Furthermore, the relationship between the composition, morphology and structural properties of MOFs with their detection capabilities for each drug species is elucidated.
  7. Kuang TK, Kang YB, Segarra I, Kanwal U, Ahsan M, Bukhari NI
    Turk J Pharm Sci, 2021 04 20;18(2):167-175.
    PMID: 33902255 DOI: 10.4274/tjps.galenos.2020.48902
    Objectives: This study was conducted to assess the effect of microwave heating on the preparation of paracetamol cross-linked gelatin matrices by using the design of experiment (DoE) approach and explore the influence of the duration of microwave irradiation, the concentrations of crosslinker, and the amount of sodium bicarbonate (salt) on paracetamol release. These parameters were also compared with those of the matrices prepared via conventional heating.

    Materials and Methods: Twenty gel matrices were prepared with different durations of microwave irradiation, amounts of maize, and concentrations of sodium bicarbonate as suggested by Design Expert (DX®). The percentage drug release, the coefficient of variance (CV) in release, and the mean dissolution time (MDT) were the properties explored in the designed experimentation.

    Results: Target responses were dependent on microwave irradiation time, cross-linker amount, and salt concentration. Classical and microwave heating did not demonstrate statistically significant difference in modifying the percentage of drug released from the matrices. However, the CVs of microwave-assisted formulations were lower than those of the gel matrices prepared via classical heating. Thus, microwave heating produced lesser variations in drug release. The optimized gel matrices demonstrated that the observed percentage of drug release, CV, and MDT were within the prediction interval generated by DX®. The release mechanism of the matrix formulations followed the Peppas-Korsmeyer anomalous transport model.

    Conclusion: The DoE-supported microwave-assisted approach could be applied to optimize the critical factors of drug release with less variation.

  8. 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.

  9. Alam MK, Alfawzan AA, Abutayyem H, Kanwal B, Alswairki HJ, Verma S, et al.
    Sci Prog, 2023;106(1):368504231156297.
    PMID: 36803068 DOI: 10.1177/00368504231156297
    The purpose of this meta-analysis was to strengthen the credibility of primary research results by combining open-source scientific material, namely a comparison of craniofacial features (Cfc) between Crouzon's syndrome (CS) patients and non-CS populations. All articles published up to October 7, 2021, were included in the search of PubMed, Google Scholar, Scopus, Medline, and Web of Science. The PRISMA guidelines were followed to conduct this study. PECO framework was applied in the following ways: Those who have CS are denoted by the letter P, those who have been diagnosed with CS via clinical or genetic means by the letter E, those who do not have CS by the letter C, and those who have a Cfc of CS by the letter O. Independent reviewers collected the data and ranked the publications based on their adherence to the Newcastle-Ottawa Quality Assessment Scale. A total of six case-control studies were reviewed for this meta-analysis. Due to the large variation in cephalometric measures, only those published in at least two previous studies were included. This analysis found that CS patients had a smaller skull and mandible volumes than those without CS.in terms of SNA° (MD = -2.33, p = <0.001, I2 = 83.6%) and ANB°(MD = -1.89, p = <0.005, I2 = 93.1%)), as well as ANS (MD = -1.87, p = 0.001, I2 = 96.5%)) and SN/PP (MD = -1.99, p = 0.036, I2 = 77.3%)). In comparison to the general population, people with CS tend to have shorter and flatter cranial bases, smaller orbital volumes, and cleft palates. They differ from the general population in having a shorter skull base and more V-shaped maxillary arches.
  10. Snider CJ, Boualam L, Tallis G, Takashima Y, Abeyasinghe R, Lo YR, et al.
    Vaccine, 2023 Apr 06;41 Suppl 1:A58-A69.
    PMID: 35337673 DOI: 10.1016/j.vaccine.2022.02.022
    Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.
  11. Mustafa ZU, Kow CS, Salman M, Kanwal M, Riaz MB, Parveen S, et al.
    Explor Res Clin Soc Pharm, 2022 Mar;5:100101.
    PMID: 34977851 DOI: 10.1016/j.rcsop.2021.100101
    Purpose: In Pakistan, a wide range of repurposed drugs are recommended to manage hospitalized patients with COVID-19. Therefore, the current study was conducted to evaluate the pattern of utilization of repurposed drugs and other potential therapeutic options among hospitalized patients with COVID-19 in Pakistan.

    Methods: This retrospective, multicenter, descriptive study enrolled consecutive hospitalized patients with COVID-19 who were admitted between March 1, 2021, and April 30, 2021, from three District Headquarter Hospitals in the Punjab province of Pakistan. We described patient and clinical characteristics and medications, stratified by COVID-19 severity during hospitalization: mild, moderate, and severe. In addition, an analytical study of drug utilization was conducted.

    Findings: A total of 444 hospitalized patients with COVID-19 were included. Remdesvir, corticosteroids, antibiotics, and antithrombotics were administered to 45.0%, 93.9%, 84.9%, and 60.1% of patients, respectively. Specifically, dexamethasone was the most commonly used corticosteroid among the included patients (n = 405; 91.2%), irrespective of their clinical severity. Only 60.1% of patients hospitalized with COVID-19 in our cohort received antithrombotic therapy, and the prevalence of use was especially low (27.8%) in patients with mild illness. Of 444 patientsscreened, 399 (89.9%) patients had been discharged, and 45 patients (10.1%) died.

    Implications: We provided an important glimpse into the utilization patterns of several medications of interest for the treatment of COVID-19 in Pakistan, which had not been entirely evidence-based, especially concerning systemic corticosteroids and antibiotics.

  12. 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.

  13. Kanwal N, Isha ASN
    Front Public Health, 2022;10:805733.
    PMID: 35372179 DOI: 10.3389/fpubh.2022.805733
    BACKGROUND: Social media activities affect every aspect of human life, be it personal, social or professional. Previous studies have confirmed the role of social media in affecting health in terms of releasing stress and providing social support. Increased occupational health disorders and increased time spent on social media activities motivate us to investigate this phenomenon in the context of occupational health. Therefore, the objective of this study is to measure the effects of social media activities related to personal and social life as well as work-life on health and wellbeing of office employees, on their job efforts and job rewards, and in moderating the effect of effort-reward imbalance on health and wellbeing.

    METHODS: Initially, to develop constructs related to social media activities, web-based structured interviews were conducted with five office employees working in the oil and gas industry for the last 5 years. Then, using an online questionnaire survey, data was collected from 424 office employees working in the oil and gas industry in Malaysia. Using statistical software for social science (SPSS) and Smart PLS, exploratory factor analysis and confirmatory factor analysis were conducted to identify reliability and validity (discriminant validity, convergent validity and composite validity) of the constructs. Following this, path analysis was conducted and the moderating effects were identified.

    RESULTS: Social media activities related to work-life decrease health and wellbeing by 11% and weaken the negative effect of effort-reward-imbalance on health and wellbeing by 17.6% at a 1% level of significance. The results of social media activities related to personal and social life strengthen the negative effect of effort-reward imbalance on health and wellbeing by 12% and negatively affects health and wellbeing and job rewards by 13, 55%, respectively. The direct effect of effort-reward imbalance and job efforts is significantly negative on health and wellbeing by 59 and 10%, respectively.

    CONCLUSION: It is concluded that social media activities of the office employees significantly moderate the effect of effort-reward imbalance on health and wellbeing and intervene in job rewards in the organizations. Hence, the effect of social media activities reduces the health and wellbeing of office employees.

  14. Rasool N, Kanwal A, Rasheed T, Ain Q, Mahmood T, Ayub K, et al.
    Int J Mol Sci, 2016;17(7).
    PMID: 27367666 DOI: 10.3390/ijms17070912
    Synthesis of 2,5-bisarylthiophenes was accomplished by sequential Suzuki cross coupling reaction of 2-bromo-5-chloro thiophenes. Density functional theory (DFT) studies were carried out at the B3LYP/6-31G(d, p) level of theory to compare the geometric parameters of 2,5-bisarylthiophenes with those from X-ray diffraction results. The synthesized compounds are screened for in vitro bacteria scavenging abilities. At the concentration of 50 and 100 μg/mL, compounds 2b, 2c, 2d, 3c, and 3f with IC50-values of 51.4, 52.10, 58.0, 56.2, and 56.5 μg/mL respectively, were found most potent against E. coli. Among all the synthesized compounds 2a, 2d, 3c, and 3e with the least values of IC50 77, 76.26, 79.13 μg/mL respectively showed significant antioxidant activities. Almost all of the compounds showed good antibacterial activity against Escherichia coli, whereas 2-chloro-5-(4-methoxyphenyl) thiophene (2b) was found most active among all synthesized compound with an IC50 value of 51.4 μg/mL. All of the synthesized compounds were screened for nitric oxide scavenging activity as well. Frontier molecular orbitals (FMOs) and molecular electrostatic potentials of the target compounds were also studied theoretically to account for their relative reactivity.
  15. Al-Mekhlafi AA, Isha ASN, Al-Quraishi MS, Kanwal N
    Front Public Health, 2023;11:1160317.
    PMID: 37869200 DOI: 10.3389/fpubh.2023.1160317
    INTRODUCTION: Driving fatigue has been shown to increase the risk of accidents and potentially fatal crashes. Fatigue is a serious risk that some drivers do not take seriously. Previous studies investigated the effects of driving fatigue in the Malaysian oil and gas transportation industry by employing survey questionnaires. However, they did not explain the behavior of fatigue. Besides, these results required validation by a more reliable method that can describe how fatigue occurs.

    METHODS: Thus, in this study, we used the Psychomotor Vigilance Test (PVT-192) and a short survey to address driving fatigue behavior and identify the influences of driving fatigue on driving performance in real life (on the road) with actual oil and gas tanker drivers. The total participants in the experimental study were 58 drivers.

    RESULTS: For the analysis, a Wilcoxon Signed Ranks Test, Z value and Spearman's rho were used to measure the significant difference between the pre and post-tests of PVT and the correlation between the fatigue variables and driving performance.

    DISCUSSION: During the experiment's first and second days, this study's results indicated that driving fatigue gradually escalated. Likewise, there was a negative correlation based on the test of the relationship between the PVT data and the driving performance survey data. Additionally, the drivers suffer from accumulative fatigue, which requires more effort from the transportation company management to promote the drivers awareness of fatigue consequences.

  16. 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.
  17. 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. 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. Kanwal, Mungroo MR, Anwar A, Ali F, Khan S, Abdullah MA, et al.
    Exp Parasitol, 2020 Nov;218:107979.
    PMID: 32866583 DOI: 10.1016/j.exppara.2020.107979
    Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.
  20. 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.
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