Displaying publications 1 - 20 of 272 in total

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  1. CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014 09 26;74(9):3036.
    PMID: 25814912
    Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
  2. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 07;74(8):2973.
    PMID: 25814904
    Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.9 fb[Formula: see text] collected with the CMS detector at the Large Hadron Collider. The measured cross sections, [Formula: see text] and [Formula: see text], are consistent with next-to-leading order quantum chromodynamics calculations.
  3. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 20;74(8):3014.
    PMID: 25814909
    The normalised differential top quark-antiquark production cross section is measured as a function of the jet multiplicity in proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] at the LHC with the CMS detector. The measurement is performed in both the dilepton and lepton+jets decay channels using data corresponding to an integrated luminosity of 5.0[Formula: see text]. Using a procedure to associate jets to decay products of the top quarks, the differential cross section of the [Formula: see text] production is determined as a function of the additional jet multiplicity in the lepton+jets channel. Furthermore, the fraction of events with no additional jets is measured in the dilepton channel, as a function of the threshold on the jet transverse momentum. The measurements are compared with predictions from perturbative quantum chromodynamics and no significant deviations are observed.
  4. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 11 12;74(11):3129.
    PMID: 25814874
    A measurement of differential cross sections for the production of a pair of isolated photons in proton-proton collisions at [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 5.0[Formula: see text] collected with the CMS detector. A data-driven isolation template method is used to extract the prompt diphoton yield. The measured cross section for two isolated photons, with transverse energy above 40 and 25[Formula: see text] respectively, in the pseudorapidity range [Formula: see text], [Formula: see text] and with an angular separation [Formula: see text], is [Formula: see text][Formula: see text]. Differential cross sections are measured as a function of the diphoton invariant mass, the diphoton transverse momentum, the azimuthal angle difference between the two photons, and the cosine of the polar angle in the Collins-Soper reference frame of the diphoton system. The results are compared to theoretical predictions at leading, next-to-leading, and next-to-next-to-leading order in quantum chromodynamics.
  5. CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014 11 26;74(11):3149.
    PMID: 25814876
    A search for heavy, right-handed neutrinos, [Formula: see text] ([Formula: see text]), and right-handed [Formula: see text] bosons, which arise in the left-right symmetric extensions of the standard model, has been performed by the CMS experiment. The search was based on a sample of two lepton plus two jet events collected in proton-proton collisions at a center-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7 [Formula: see text]. For models with strict left-right symmetry, and assuming only one [Formula: see text] flavor contributes significantly to the [Formula: see text] decay width, the region in the two-dimensional [Formula: see text] mass plane excluded at a 95 % confidence level extends to approximately [Formula: see text] and covers a large range of neutrino masses below the [Formula: see text] boson mass, depending on the value of [Formula: see text]. This search significantly extends the [Formula: see text] exclusion region beyond previous results.
  6. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2020;80(3):189.
    PMID: 32226948 DOI: 10.1140/epjc/s10052-020-7739-7
    A search is presented for τ slepton pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV . The search is carried out in events containing two τ leptons in the final state, on the assumption that each τ slepton decays primarily to a τ lepton and a neutralino. Events are considered in which each τ lepton decays to one or more hadrons and a neutrino, or in which one of the τ leptons decays instead to an electron or a muon and two neutrinos. The data, collected with the CMS detector in 2016 and 2017, correspond to an integrated luminosity of 77.2 fb - 1 . The observed data are consistent with the standard model background expectation. The results are used to set 95% confidence level upper limits on the cross section for τ slepton pair production in various models for τ slepton masses between 90 and 200 GeV and neutralino masses of 1, 10, and 20 GeV . In the case of purely left-handed τ slepton production and decay to a τ lepton and a neutralino with a mass of 1 GeV , the strongest limit is obtained for a τ slepton mass of 125 GeV at a factor of 1.14 larger than the theoretical cross section.
  7. Soon SS, Chia WK, Chan ML, Ho GF, Jian X, Deng YH, et al.
    PLoS One, 2014;9(9):e107866.
    PMID: 25250815 DOI: 10.1371/journal.pone.0107866
    Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older.
  8. Kamaruzaman NH, Mohd Noor NN, Radin Mohamed RMS, Al-Gheethi A, Ponnusamy SK, Sharma A, et al.
    Environ Res, 2022 Feb 03;209:112831.
    PMID: 35123962 DOI: 10.1016/j.envres.2022.112831
    The abundance of antibiotic-resistant bacteria in the prawn pond effluents can substantially impact the natural environment. The settlement ponds, which are the most common treatment method for farms wastewater, might effectively reduce the suspended solids and organic matter. However, the method is insufficient for bacterial inactivation. The current paper seeks to highlight the environmental issue associated with the distribution of antibiotic resistant bacteria (ARB) from prawn farm wastewater and their impact on the microbial complex community in the surface water which receiving these wastes. The inactivation of antibiotic-resistant bacteria in prawn wastewater is strongly recommended because the presence of antibiotic-resistant bacteria in the environment causes water pollution and public health issues. The nanoparticles are more efficient for bacterial inactivation. They are widely accepted due to their high chemical and mechanical stability, broad spectrum of radiation absorption, high catalytic activity, and high antimicrobial activity. Many studies have examined the use of fungi or plants extract to synthesis zinc oxide nanoparticles (ZnO NPs). It is evident from recent papers in the literature that green synthesized ZnO NPs from microbes and plant extracts are non-toxic and effective. ZnO NPs inactivate the bacterial cells as a function for releasing reactive oxygen species (ROS) and zinc ions. The inactivation of antibiotic-resistant bacteria tends to be more than 90% which exhibit strong antimicrobial behavior against bacterial species.
  9. Nguyen HT, Nguyen HT, Ahmed SF, Rajamohan N, Yusuf M, Sharma A, et al.
    Environ Res, 2023 Mar 30;227:115800.
    PMID: 37003549 DOI: 10.1016/j.envres.2023.115800
    The considerable increase in world energy consumption owing to rising global population, intercontinental transportation and industrialization has posed numerous environmental concerns. Particularly, in order to meet the required electricity supply, thermal power plants for electricity generation are widely used in many countries. However, an annually excessive quantity of waste fly ash up to 1 billion tones was globally discarded from the combustion of various carbon-containing feedstocks in thermoelectricity plants. About half of the industrially generated fly ash is dumped into landfills and hence causing soil and water contamination. Nonetheless, fly ash still contains many valuable components and possesses outstanding physicochemical properties. Utilizing waste fly ash for producing value-added products has gained significant interests. Therefore, in this work, we reviewed the current implementation of fly ash-derived materials, namely, zeolite and geopolymer as efficient adsorbents for the environmental treatment of flue gas and polluted water. Additionally, the usage of fly ash as a catalyst support for the photodegradation of organic pollutants and reforming processes for the corresponding wastewater remediation and H2 energy generation is thoroughly covered. In comparison with conventional carbon-based adsorbents, fly ash-derived geopolymer and zeolite materials reportedly exhibited greater heavy metal ions removal and reached the maximum adsorption capacity of about 150 mg g-1. As a support for biogas reforming process, fly ash could enhance the activity of Ni catalyst with 96% and 97% of CO2 and CH4 conversions, respectively.
  10. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(7):629.
    PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z
    Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
  11. Sirunyan AM, CMS Collaboration, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(1):13.
    PMID: 33493254 DOI: 10.1140/epjc/s10052-020-08739-5
    A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
  12. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(6):488.
    PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x
    Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
  13. Hai T, Alshahri AH, Mohammed AS, Sharma A, Almujibah HR, Mohammed Metwally AS, et al.
    Chemosphere, 2023 Sep;334:138980.
    PMID: 37207897 DOI: 10.1016/j.chemosphere.2023.138980
    The use of renewable fuels leads to reduction in the use of fossil fuels and environmental pollutants. In this study, the design and analysis of a CCPP based on the use of syngas produced from biomass is discussed. The studied system includes a gasifier system to produce syngas, an external combustion gas turbine and a steam cycle to recover waste heat from combustion gases. Design variables include syngas temperature, syngas moisture content, CPR, TIT, HRSG operating pressure, and PPTD. The effect of design variables on performance components such as power generation, exergy efficiency and total cost rate of the system is investigated. Also, through multi-objective optimization, the optimal design of the system is done. Finally, it is observed that at the final decisioned optimal point, the produced power is 13.4 MW, the exergy efficiency is 17.2%, and the TCR is 118.8 $/h.
  14. Kumar R, Khan FU, Sharma A, Siddiqui MH, Aziz IB, Kamal MA, et al.
    Environ Sci Pollut Res Int, 2021 Sep;28(34):47641-47650.
    PMID: 33895950 DOI: 10.1007/s11356-021-14028-9
    We are exposed to various chemical compounds present in the environment, cosmetics, and drugs almost every day. Mutagenicity is a valuable property that plays a significant role in establishing a chemical compound's safety. Exposure and handling of mutagenic chemicals in the environment pose a high health risk; therefore, identification and screening of these chemicals are essential. Considering the time constraints and the pressure to avoid laboratory animals' use, the shift to alternative methodologies that can establish a rapid and cost-effective detection without undue over-conservation seems critical. In this regard, computational detection and identification of the mutagens in environmental samples like drugs, pesticides, dyes, reagents, wastewater, cosmetics, and other substances is vital. From the last two decades, there have been numerous efforts to develop the prediction models for mutagenicity, and by far, machine learning methods have demonstrated some noteworthy performance and reliability. However, the accuracy of such prediction models has always been one of the major concerns for the researchers working in this area. The mutagenicity prediction models were developed using deep neural network (DNN), support vector machine, k-nearest neighbor, and random forest. The developed classifiers were based on 3039 compounds and validated on 1014 compounds; each of them encoded with 1597 molecular feature vectors. DNN-based prediction model yielded highest prediction accuracy of 92.95% and 83.81% with the training and test data, respectively. The area under the receiver's operating curve and precision-recall curve values were found to be 0.894 and 0.838, respectively. The DNN-based classifier not only fits the data with better performance as compared to traditional machine learning algorithms, viz., support vector machine, k-nearest neighbor, and random forest (with and without feature reduction) but also yields better performance metrics. In current work, we propose a DNN-based model to predict mutagenicity of compounds.
  15. Aljabali AAA, Bakshi HA, Satija S, Metha M, Prasher P, Ennab RM, et al.
    Pharm Nanotechnol, 2020;8(4):323-353.
    PMID: 32811406 DOI: 10.2174/2211738508999200817163335
    BACKGROUND: The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.

    OBJECTIVES: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.

    METHODS: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.

    RESULTS: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures.

    Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.

  16. Huy NT, Chico RM, Huan VT, Shaikhkhalil HW, Uyen VNT, Qarawi ATA, et al.
    PLoS One, 2021;16(12):e0258348.
    PMID: 34936646 DOI: 10.1371/journal.pone.0258348
    BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave.

    METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training.

    RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors.

    INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type.

  17. Kanneganti A, Tan BYQ, Nik Ab Rahman NH, Leow AS, Denning M, Goh ET, et al.
    Singapore Med J, 2023 Nov;64(11):667-676.
    PMID: 35139631 DOI: 10.11622/smedj.2022014
    INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety.

    METHODS: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR).

    RESULTS: We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR.

    CONCLUSION: Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.

  18. Jha NK, Sharma A, Jha SK, Ojha S, Chellappan DK, Gupta G, et al.
    Open Biol, 2020 12;10(12):200286.
    PMID: 33352062 DOI: 10.1098/rsob.200286
    Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.
  19. Sharma A, Sikka M, Bhankar H, Gomber S, Sharma S
    Malays J Pathol, 2017 Aug;39(2):155-159.
    PMID: 28866697
    Sepsis is a common cause of death in infants and children. Haemostatic abnormalities have been reported in such patients. There is scant information on the nature and frequency of these abnormalities in children especially from India. Our aim was to evaluate the nature and frequency of haematological and haemostatic abnormalities in children with sepsis. Fifty children between 1-10 years of age admitted with sepsis and 50 age-matched, healthy controls were included in the study. Complete blood counts, examination of stained peripheral blood film, prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen, C-reactive protein, liver function tests and serum creatinine were done in all patients and controls. Prolonged PT and APTT were seen in 9 (18%) and 24 (48%) patients respectively. Plasma fibrinogen was decreased in 6% and increased in 8% patients. One or more haemostatic parameter was abnormal in 35 (70%) patients and in all patients who died.
  20. Monika, Sharma A, Suthar SK, Aggarwal V, Lee HB, Sharma M
    Bioorg Med Chem Lett, 2014 Aug 15;24(16):3814-8.
    PMID: 25027934 DOI: 10.1016/j.bmcl.2014.06.068
    The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
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