Displaying publications 61 - 80 of 91 in total

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  1. Majid Shah S, Ullah F, Ayaz M, Sadiq A, Hussain S, Ali Shah AU, et al.
    Steroids, 2019 08;148:56-62.
    PMID: 31085212 DOI: 10.1016/j.steroids.2019.05.001
    The current study was aimed to evaluate the anti-leishmanial potentials of β-sitosterol isolated from Ifloga spicata. The anti-leishmanial potential of β-sitosterol is well documented against Leishmania donovani and Leishmania amazonensis but unexplored against Leishmania tropica. Structure of the compound was elucidated by FT-IR, mass spectrometry and multinuclear (1H and 13C) magnetic resonance spectroscopy. The compound was evaluated for its anti-leishmanial potentials against L. tropica KWH23 using in vitro anti-promastigote, DNA interaction, apoptosis, docking studies against leishmanolysin (GP63) and trypanothione reductase (TR) receptors using MOE 2016 software. β-sitosterol exhibited significant activity against leishmania promastigotes with IC50 values of 9.2 ± 0.06 μg/mL. The standard drug glucantaime showed IC50 of 5.33 ± 0.07 µg/mL. Further mechanistic studies including DNA targeting and apoptosis induction via acridine orange assay exhibited promising anti-leishmanial potentials for β-sitosterol. Molecular docking with leishmanolysin (GP63) and trypanothione reductase (TR) receptors displayed the binding scores of β-sitosterol with targets TR and GP63 were -7.659 and -6.966 respectively. The low binding energies -61.54 (for TR) and -33.24 (for GP63) indicate that it strongly bind to the active sites of target receptors. The results confirmed that β-sitosterol have considerable anti-leishmanial potentials and need further studies as potential natural anti-leishmanial agent against L. tropica.
  2. Zulkipli AF, Islam T, Mohd Taib NA, Dahlui M, Bhoo-Pathy N, Al-Sadat N, et al.
    Integr Cancer Ther, 2018 06;17(2):312-321.
    PMID: 29218996 DOI: 10.1177/1534735417745248
    BACKGROUND: The use of complementary and alternative medicine (CAM) has increased and little is known on CAM use during the initial period. Therefore, the aim was to determine prevalence of CAM use among newly diagnosed breast cancer patients prior to seeking conventional treatment.

    METHODS: This is a cross-sectional study involved interviewing newly diagnosed breast cancer patients in the University Malaya Medical Centre (UMMC) using a structured questionnaire. Eligible respondents were interviewedduring a routine clinical visit.

    RESULTS: A total of 400 patients were interviewed, of whom 139 (34.8%) were CAM users. Dietary supplementation (n = 107, 77.0%) was the most frequently used type of CAM, followed by spiritual healing (n = 40, 28.8%) and traditional Chinese medicine (n = 32, 23.0%). Malay ethnic group (n = 61, 43.9%) was the largest group of CAM users, followed by Chinese (n = 57, 41.0%) and Indian (n = 20, 14.4%). Majority of these CAM users (n = 87, 73.1%) did not disclose the use of CAM to their doctors. Most of them used remedies based on the recommendation of family and friends. Malay ethnicity and patients with 3 or more comorbidities were more likely to use CAM.

    CONCLUSION: There is substantial use of CAM among breast cancer patients in UMMC prior to seeking hospital treatment, and the most popular CAM modality is dietary supplements. Since, the majority of CAM users do not disclose the use of CAM to their physicians, therefore health care providers should ensure that those patients who are likely to use CAM are appropriately counseled and advised.

  3. Inayat-Hussain SH, Wong LT, Chan KM, Rajab NF, Din LB, Harun R, et al.
    Toxicol Lett, 2009 Dec 15;191(2-3):118-22.
    PMID: 19698770 DOI: 10.1016/j.toxlet.2009.08.012
    Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Overexpression of full-length receptor for activated protein C-kinase 1 (RACK-1) and pc3n3, which up-regulates endogenous RACK-1, in both Jurkat and W7.2 T cells resulted in inhibition of goniothalamin-induced cell death as assessed by MTT and clonogenic assays. However, overexpression of rFau (antisense sequence to Finkel-Biskis-Reilly murine sarcoma virus-associated ubiquitously expressed gene) in W7.2 cells did not confer resistance to goniothalamin-induced cell death. Etoposide, a clinically used cytotoxic agent, was equipotent in causing cytotoxicity in all the stable transfectants. Assessment of DNA damage by Comet assay revealed goniothalamin-induced DNA strand breaks as early as 1 h in vector control but this effect was inhibited in RACK-1 and pc3n3 stably transfected W7.2 cells. This data demonstrate that RACK-1 plays a crucial role in regulating cell death signalling pathways induced by goniothalamin.
  4. Hussain S, Javed W, Tajammal A, Khalid M, Rasool N, Riaz M, et al.
    ACS Omega, 2023 May 16;8(19):16600-16611.
    PMID: 37214690 DOI: 10.1021/acsomega.2c06785
    Current studies were performed to investigate the phytochemistry, synergistic antibacterial, antioxidant, and hemolytic activities of ethanolic and aqueous extracts of Azadirachta indica (EA and WA) and Cymbopogon citratus (EC and WC) leaves. Fourier transform infrared data verified the existence of alcoholic, carboxylic, aldehydic, phenyl, and bromo moieties in plant leaves. The ethanolic extracts (EA and EC) were significantly richer in phenolics and flavonoids as compared to the aqueous extracts (WA and WC). The ethanolic extract of C. citratus (EC) contained higher concentrations of caffeic acid (1.432 mg/g), synapic acid (6.743 mg/g), and benzoic acid (7.431 mg/g) as compared to all other extracts, whereas chlorogenic acid (0.311 mg/g) was present only in the aqueous extract of A. indica (WA). Food preservative properties of C. citratus can be due to the presence of benzoic acid (7.431 mg/g). -Gas chromatography-mass spectrometry analysis demonstrated the presence of 36 and 23 compounds in A. indica and C. citratus leaves, respectively. Inductively coupled plasma analysis was used to determine the concentration of 26 metals (Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Si, Sn, Sr, V, Zn, Zr, Ti); the metal concentrations were higher in aqueous extracts as compared to the ethanolic extracts. The extracts were generally richer in calcium (3000-7858 ppm), potassium (13662-53,750 ppm), and sodium (3181-8445 ppm) and hence can be used in food supplements as a source of these metals. Antioxidant potential (DDPH method) of C. citratus ethanolic extract was the highest (74.50 ± 0.66%), whereas it was the lowest (32.22 ± 0.28%) for the aqueous extract of A. indica. Synergistic inhibition of bacteria (Staphylococcus aureus and Escherichia coli) was observed when the aqueous extracts of both the plants were mixed together in certain ratios (v/v). The highest antibacterial potential was exhibited by the pure extract of C. citratus, which was even higher than that of the standard drug (ciprofloxacin). The plant extracts and their mixtures were more active against S. aureus as compared to E. coli. No toxic hemolytic effects were observed for the investigated extracts indicating their safe medicinal uses for human beings.
  5. Masand VH, Al-Hussain S, Alzahrani AY, El-Sayed NNE, Yeo CI, Tan YS, et al.
    Expert Opin Drug Discov, 2024;19(1):111-124.
    PMID: 37811790 DOI: 10.1080/17460441.2023.2266990
    BACKGROUND: The process of drug development and discovery is costly and slow. Although an understanding of molecular design principles and biochemical processes has progressed, it is essential to minimize synthesis-testing cycles. An effective approach is to analyze key heteroatoms, including oxygen and nitrogen. Herein, we present an analysis focusing on the utilization of nitrogen atoms in approved drugs.

    RESEARCH DESIGN AND METHODS: The present work examines the frequency, distribution, prevalence, and diversity of nitrogen atoms in a dataset comprising 2,049 small molecules approved by different regulatory agencies (FDA and others). Various types of nitrogen atoms, such as sp3-, sp2-, sp-hybridized, planar, ring, and non-ring are included in this investigation.

    RESULTS: The results unveil both previously reported and newly discovered patterns of nitrogen atom distribution around the center of mass in the majority of drug molecules.

    CONCLUSIONS: This study has highlighted intriguing trends in the role of nitrogen atoms in drug design and development. The majority of drugs contain 1-3 nitrogen atoms within 5Å from the center of mass (COM) of a molecule, with a higher preference for the ring and planar nitrogen atoms. The results offer invaluable guidance for the multiparameter optimization process, thus significantly contributing toward the conversion of lead compounds into potential drug candidates.

  6. Khalid MF, Hussain S, Anjum MA, Morillon R, Ahmad S, Ejaz S, et al.
    PLoS One, 2021;16(4):e0247558.
    PMID: 33831006 DOI: 10.1371/journal.pone.0247558
    Water shortage is among the major abiotic stresses that restrict growth and productivity of citrus. The existing literature indicates that tetraploid rootstocks had better water-deficit tolerance than corresponding diploids. However, the associated tolerance mechanisms such as antioxidant defence and nutrient uptake are less explored. Therefore, we evaluated physiological and biochemical responses (antioxidant defence, osmotic adjustments and nutrient uptake) of diploid (2x) and tetraploid (4x) volkamer lemon (VM) rootstocks grafted with kinnow mandarin (KM) under two water-deficit regimes. The KM/4xVM (VM4) and KM/2xVM (VM2) observed decrease in photosynthetic variables, i.e., photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (E), leaf greenness (SPAD), dark adopted chlorophyll fluorescence (Fv/Fm), dark adopted chlorophyll fluorescence (Fv´/Fm´), relative water contents (RWC) and leaf surface area (LSA), and increase in non-photochemical quenching (NPQ) under both water-deficit regimes. Moreover, oxidative stress indicators, i.e., malondialdehyde (MDA) and hydrogen peroxide, and activities of antioxidant enzymes, i.e., superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APx), glutathione reductase (GR) were increased under both water-deficit regimes. Nonetheless, increase was noted in osmoprotectants such as proline (PRO) and glycine betaine (GB) and other biochemical compounds, including antioxidant capacity (AC), total phenolic content (TPC) and total soluble protein (TSP) in VM2 and VM4 under both water-deficit regimes. Dry biomass (DB) of both rootstocks was decreased under each water-deficit condition. Interestingly, VM4 showed higher and significant increase in antioxidant enzymes, osmoprotectants and other biochemical compounds, while VM2 exhibited higher values for oxidative stress indicators. Overall, results indicated that VM4 better tolerated water-deficit stress by maintaining photosynthetic variables associated with strong antioxidant defence machinery as compared to VM2. However, nutrient uptake was not differed among tested water-deficit conditions and rootstocks. The results conclude that VM4 can better tolerate water-deficit than VM2. Therefore, VM4 can be used as rootstock in areas of high-water deficiency for better citrus productivity.
  7. Kumar N, Sheikh Ghadzi SM, Rajpoot PL, Thanganadar H, Hashmi FK, Noor A, et al.
    J Infect Dev Ctries, 2024 Feb 29;18(2):177-187.
    PMID: 38484345 DOI: 10.3855/jidc.18313
    INTRODUCTION: Hypertension significantly contributes to the severity and mortality of COVID-19 patients. It has also been a risk factor for prolonged hospitalization and the need for intensive care. However, the data is still evolving. Therefore, this study investigated the predictors of mortality among hypertensive COVID-19 patients.

    METHODOLOGY: A single-center cohort study was performed at Indus Hospital and Health Network, Karachi, Pakistan, between April 1, 2021, and October 31, 2021. This study included 333 hospitalized hypertensive COVID-19 patients and evaluated their clinical characteristics and survival outcomes. A multivariate logistic regression model was applied in IBM SPSS 27.0 to determine the predictors of mortality.

    RESULTS: The majority of patients were females (54.7%), the median age was 62 [55-70] years, with co-existing diabetes (56.5%) and severely ill (52.6%). The independent predictors of mortality identified were age ≥ 65 years (aOR 20.89, 95% CI, 5.81-75.15; p < 0.001), pulse rate (aOR 1.03, 95% CI 1.01-1.63; p = 0.006), serum creatinine (aOR 1.34, 95% CI 1.11-1.63; p = 0.002), use of antibiotics (aOR 3.40, 95% CI 1.29-8.98; p = 0.014)), corticosteroid (aOR 49.68, 95% CI 1.83-1350.31; p = 0.020), and who needed high flow oxygen supply (aOR 13.08, 95% CI 1.70-100.54; p < 0.001), non-invasive mechanical ventilation (aOR 229.01, 95% CI 29.30-1789.71; p < 0.001) and invasive mechanical ventilation (aOR 379.54, 95% CI 36.60-3935.87; p < 0.001).

    CONCLUSIONS: Our study suggests that older age, elevated pulse rate, serum creatinine, use of antibiotics and corticosteroids, and the need for mechanical ventilation predict mortality among hypertensive COVID-19.

  8. Chee ZJ, Chang CYM, Cheong JY, Malek FHBA, Hussain S, de Vries M, et al.
    Int J Psychophysiol, 2024 May;199:112328.
    PMID: 38458383 DOI: 10.1016/j.ijpsycho.2024.112328
    According to the arousal-mood hypothesis, changes in arousal and mood when exposed to auditory stimulation underlie the detrimental effects or improvements in cognitive performance. Findings supporting or against this hypothesis are, however, often based on subjective ratings of arousal rather than autonomic/physiological indices of arousal. To assess the arousal-mood hypothesis, we carried out a systematic review of the literature on 31 studies investigating cardiac, electrodermal, and pupillometry measures when exposed to different types of auditory stimulation (music, ambient noise, white noise, and binaural beats) in relation to cognitive performance. Our review suggests that the effects of music, noise, or binaural beats on cardiac, electrodermal, and pupillometry measures in relation to cognitive performance are either mixed or insufficient to draw conclusions. Importantly, the evidence for or against the arousal-mood hypothesis is at best indirect because autonomic arousal and cognitive performance are often considered separately. Future research is needed to directly evaluate the effects of auditory stimulation on autonomic arousal and cognitive performance holistically.
  9. Rahim F, Ullah K, Ullah H, Wadood A, Taha M, Ur Rehman A, et al.
    Bioorg Chem, 2015 Feb;58:81-7.
    PMID: 25528720 DOI: 10.1016/j.bioorg.2014.12.001
    A new series of triazinoindole analogs 1-11 were synthesized, characterized by EI-MS and (1)H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC50 value ranging between 2.46±0.008 and 312.79±0.06 μM when compared with the standard acarbose (IC50, 38.25±0.12 μM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC50 values 2.46±0.008, 37.78±0.05, 28.91±0.0, 38.12±0.04, 37.43±0.03, 36.89±0.06 and 37.11±0.05 μM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.
  10. Islam T, Bhoo-Pathy N, Su TT, Majid HA, Nahar AM, Ng CG, et al.
    BMJ Open, 2015 Oct 26;5(10):e008643.
    PMID: 26503386 DOI: 10.1136/bmjopen-2015-008643
    INTRODUCTION: Over recent decades, the burden of breast cancer has been increasing at an alarming rate in Asia. Prognostic research findings from Western countries may not readily be adapted to Asia, as the outcome of breast cancer depends on a multitude of factors ranging from genetic, clinical and histological predictors, to lifestyle and social predictors. The primary aim of this study is to determine the impact of lifestyle (eg, nutrition, physical activity), mental and sociocultural condition, on the overall survival and quality of life (QoL) among multiethnic Malaysian women following diagnosis of breast cancer. This study aims to advance the evidence on prognostic factors of breast cancer within the Asian setting. The findings may guide management of patients with breast cancer not only during active treatment but also during the survivorship period.

    METHODS: This hospital-based prospective cohort study will comprise patients with breast cancer (18 years and above), managed in the University Malaya Medical Centre (UMMC). We aim to recruit 1000 cancer survivors over a 6-year period. Data collection will occur at baseline (within 3 months of diagnosis), 6 months, and 1, 3 and 5 years following diagnosis. The primary outcomes are disease-free survival and overall survival, and secondary outcome is QoL. Factors measured are demographic and socioeconomic factors, lifestyle factors (eg, dietary intake, physical activity), anthropometry measurements (eg, height, weight, waist, hip circumference, body fat analysis), psychosocial aspects, and complementary and alternative medicine (CAM) usage.

    ETHICS AND DISSEMINATION: This protocol was approved by the UMMC Ethical Committee in January 2012. All participants are required to provide written informed consent. The findings from our cohort study will be disseminated via scientific publication as well as presentation to stakeholders including the patients, clinicians, the public and policymakers, via appropriate avenues.

  11. Rahim F, Ullah H, Javid MT, Wadood A, Taha M, Ashraf M, et al.
    Bioorg Chem, 2015 Oct;62:15-21.
    PMID: 26162519 DOI: 10.1016/j.bioorg.2015.06.006
    A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed good α-glucosidase inhibitory activity with IC50 value ranging between 18.23±0.03 and 424.41±0.94μM when compared with the standard acarbose (IC50, 38.25±0.12μM). Compound (8) (IC50, 18.23±0.03μM) and compound (7) (IC50=36.75±0.05μM) exhibited outstanding inhibitory potential much better than the standard acarbose (IC50, 38.25±0.12μM). All other analogs also showed good to moderate enzyme inhibition. Molecular docking studies were carried out in order to find the binding affinity of thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of α-glucosidase inhibitors.
  12. Harizt AM, Malahubban M, Syed-Hussain SS, Ramanoon SZ, Sadiq MB, Sarbini SR, et al.
    Trop Biomed, 2021 Sep 01;38(3):318-326.
    PMID: 34508339 DOI: 10.47665/tb.38.3.072
    The objectives of this study were to investigate the prevalence and associated risk factors for gastrointestinal (GI) parasites in buffaloes from various areas of Sarawak, and to assess current management practices of GI parasites among farmers. Faecal samples were collected from 15 farms and 129 animals, as well as data on farm and animal-based characteristics. A total of 129 faecal samples were examined for GI parasites using a modified McMaster and sedimentation. Association between potential risk factors and the prevalence of GI parasites was investigated using Chi-square statistic. The prevalence of Paramphistomum sp., strongyles, and coccidia were 75.2% (95% CI±7.5), 52.7% (95% CI±8.6) and 48.1% (95% CI±8.6), respectively. Farms which had a grazing area less than 50 acres in size had significantly higher prevalence of strongyles (70.5%, χ2 = 8.34, P = 0.004) and paramphistomes (88.6%, χ2 = 6.46, P = 0.01) relative to farms with a larger grazing area (43.5% and 68.2%, respectively). Prevalence of strongyles was lower in farms that did not implement a cut- and-carry system (45.6%, χ2 = 4.17, P = 0.04) in comparison to those that did (64%). The prevalence of paramphistomes was higher on farms with more than 40 animals (80.6%, χ2 = 3.18, P = 0.05) relative to farms with fewer animals. The majority of farmers surveyed (67.9%) showed awareness of GI parasite infection and reported that they recognized the associated symptoms. Most farmers practised deworming, and ivermectin was the most commonly used anthelminthic (60.4%); only 1.9% of farmers used albendazole. Overall this study revealed a high prevalence of GI parasites in buffalo in Sarawak. Although farmers report they are aware of parasitic diseases, further education is still required. This could include how they can successfully implement on-farm changes to reduce the prevalence of GI parasites in their herds.
  13. Alomari M, Taha M, Rahim F, Selvaraj M, Iqbal N, Chigurupati S, et al.
    Bioorg Chem, 2021 03;108:104638.
    PMID: 33508679 DOI: 10.1016/j.bioorg.2021.104638
    A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1HNMR, 13C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC50 = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.
  14. Sadiq MB, Syed-Hussain SS, Ramanoon SZ, Saharee AA, Ahmad NI, Mohd Zin N, et al.
    Prev Vet Med, 2018 Aug 01;156:76-83.
    PMID: 29891148 DOI: 10.1016/j.prevetmed.2018.04.013
    The increasing public health problem of antimicrobial resistance (AMR) has been linked to the extensive antimicrobial use (AMU) in food animals. We conducted a survey among ruminant farmers in Selangor, Malaysia to assess their level of awareness on AMR, attitudes towards AMU, and determinants that influence their practices. The survey was developed in English and Malay, validated, and administered to ruminant farmers in Selangor. A total of 84 farmers (response rate of 55%) completed the structured questionnaire. They appeared to be little aware of AMR and the impact on animals and public health. Indications of inappropriate AMU include their misconception on conditions requiring antibiotic therapy and easy accessibility to antibiotics. More than 70% (60/84) of the respondents believed that all sick animals need to be given antimicrobials. Half of the farmers especially those involved in the production of small and large ruminants; namely mixed ruminant farmers (MRF) (63%, 31/49) indicated that antimicrobials do not have any side effects in animals. Sixty-four percent (54/84) of the farmers have stored antimicrobials in their farms of which the practice was more common (P = 0.02) among the MRF compared to the single ruminant farmers (SRF). Although most of the farmers felt good farm biosecurity will help reduce AMU, they were indifferent regarding using antimicrobials only when prescribed by a veterinarian and non-storage of antimicrobials for later uses. Farmers with larger herd size (>100 animals/herd) and few years of farming experience agreed more to the suggestions about their role and that of veterinarians respectively in reducing the drivers of AMR. These areas might need to be considered by advisors to inform ruminant farmers on AMR and to encourage them for prudent AMU in food-producing animals.
  15. Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al.
    Bioorg Chem, 2017 06;72:21-31.
    PMID: 28346872 DOI: 10.1016/j.bioorg.2017.03.007
    On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
  16. Hussain S, Ullah F, Sadiq A, Ayaz M, Shah AA, Ali Shah SA, et al.
    Curr Top Med Chem, 2019;19(30):2805-2813.
    PMID: 31702502 DOI: 10.2174/1568026619666191105103801
    BACKGROUND: Liver cancer is a devastating cancer with increasing incidence and mortality rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally occurring cytotoxic compounds is urgently needed.

    METHODS: The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A. arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated by performing Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine kinase.

    RESULTS: In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9 μg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest antiproliferative activity with IC50 6.55 ± 1.2 μg/ml followed by ethyl acetate (Aa.Et) fraction (IC50, 24.59 ± 0.85 μg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5μg/ml). However, the aqueous (Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation of two compounds which were characterized as para-methoxycatechol (1) and decane (2) through various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50 6.03 ± 0.75 μg/ml followed by 2 with IC50 18.52 ± 1.9 μg/ml. DMSO was used as a negative control and doxorubicin as a reference standard (IC50 1.3 ± 0.21 μg/ml). It was observed that compounds 1-2 caused apoptotic cell death evaluated by Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine kinase to support cytotoxic activity.

    CONCLUSION: This study revealed that the plant extracts and isolated compounds possess promising antiproliferative activity against HepG-2 cell lines via apoptotic cell death.

  17. Hussain S, Ullah F, Ayaz M, Ali Shah SA, Ali Shah AU, Shah SM, et al.
    Drug Des Devel Ther, 2019;13:4195-4205.
    PMID: 31849451 DOI: 10.2147/DDDT.S228971
    Background: Cancer is one of the chronic health conditions worldwide. Various therapeutically active compounds from medicinal plants were the current focus of this research in order to uncover a treatment regimen for cancer. Anchusa arvensis (A. anchusa) (L.) M.Bieb. contains many biologically active compounds.

    Methods: In the current study, new ester 3-hydroxyoctyl -5- trans-docosenoate (compound-1) was isolated from the chloroform soluble fraction of A. anchusa using column chromatography. Using MTT assay, the anticancer effect of the compound was determined in human hepatocellular carcinoma cells (HepG-2) compared with normal epithelial cell line (Vero). DPPH and ABTS radical scavenging assays were performed to assess the antioxidant potential. The Molecular Operating Environment (MOE-2016) tool was used against tyrosine kinase.

    Results: The structure of the compound was elucidated based on IR, EI, and NMR spectroscopy technique. It exhibited a considerable cytotoxic effect against HepG-2 cell lines with IC50 value of 6.50 ± 0.70 µg/mL in comparison to positive control (doxorubicin) which showed IC50 value of 1.3±0.21 µg/mL. The compound did not show a cytotoxic effect against normal epithelial cell line (Vero). The compound also exhibited significant DPHH scavenging ability with IC50 value of 12 ± 0.80 µg/mL, whereas ascorbic acid, used as positive control, demonstrated activity with IC50 = 05 ± 0.15 µg/mL. Similarly, it showed ABTS radical scavenging ability (IC50 = 130 ± 0.20 µg/mL) compared with the value obtained for ascorbic acid (06 ± 0.85 µg/mL). In docking studies using MOE-2016 tool, it was observed that compound-1 was highly bound to tyrosine kinase by having two hydrogen bonds at the hinge region. This good bonding network by the compound might be one of the reasons for showing significant activity against this enzyme.

    Conclusion: Our findings led to the isolation of a new compound from A. anchusa which has significant cytotoxic activity against HepG-2 cell lines with marked antioxidant potential.

  18. Shah N, Khan A, Ali R, Marimuthu K, Uddin MN, Rizwan M, et al.
    Biomed Res Int, 2020;2020:6185231.
    PMID: 32382561 DOI: 10.1155/2020/6185231
    Health and environmental problems arising from metals present in the aquatic ecosystem are very well known. The present study investigated toxicological effects of LC15 of metals such as copper, chromium, and lead for 24, 48, 72, and 96 h on hematological indices, RBC nucleus and cell morphology, and gill and muscle tissues of grass carp (Ctenopharyngodon idella). Experimental dose concentrations of copper were 1.5, 1.4, 1.2, and 1 mgL-1. Similarly, dose concentrations of chromium were 25.5, 22.5, 20, and 18 mgL-1 while those of lead were 250, 235, 225, and 216 mgL-1, respectively. Maximum decrease in the concentration of Hb, RBCs, and monocytes was observed against chromium, while maximum increase in the concentration of lymphocytes was reported against lead. Abnormalities such as single and double micronuclei, deformed nucleus, nuclear shift, irregular nucleus, deformed cells, microcyte cells, and vacuolated and swollen cells were observed. Gill tissues absorbed maximum concentration of lead followed by chromium and copper. Muscle tissues also absorbed maximum concentration of lead followed by chromium and copper, respectively. Histological alterations such as epithelial lifting, interlamellar spaces, club gill filaments, gill bridging, curling filaments, swelling and fusion of cells, irregular cells, destruction of epithelial cells, cellular necrosis, and inflammatory cells were observed in gill tissues while inflammation and necrosis of muscle fibers, degeneration of muscle fibers, edema of muscle bundles, zig-zag of muscle fibers, and lesions were observed in muscle tissues of fish exposed with different doses of these heavy metals, indicating the toxicity of metals to aquatic fauna as well as to human being via food chain.
  19. Khan A, Hussain S, Ahmad S, Suleman M, Bukhari I, Khan T, et al.
    Comput Biol Med, 2022 02;141:105163.
    PMID: 34979405 DOI: 10.1016/j.compbiomed.2021.105163
    The spike protein of SARS-CoV-2 and the host ACE2 receptor plays a vital role in the entry to the cell. Among which the hotspot residue 501 is continuously subjected to positive selection pressure and induces unusual virulence. Keeping in view the importance of the hot spot residue 501, we predicted the potentially emerging structural variants of 501 residue. We analyzed the binding pattern of wild type and mutants (Spike RBD) to the ACE2 receptor by deciphering variations in the amino acids' interaction networks by graph kernels along with evolutionary, network metrics, and energetic information. Our analysis revealed that N501I, N501T, and N501V increase the binding affinity and alter the intra and inter-residue bonding networks. The N501T has shown strong positive selection and fitness in other animals. Docking results and repeated simulations (three times) confirmed the structural stability and tighter binding of these three variants, correlated with the previous results following the global stability trend. Consequently, we reported three variants N501I, N501T, and N501V could worsen the situation further if they emerged. The relations between the viral fitness and binding affinity is a complicated game thus the emergence of high affinity mutations in the SARS-CoV-2 RBD brings up the question of whether or not positive selection favours these mutations or not?
  20. Shahzad MK, Hussain S, Farooq MU, Laghari RA, Bilal MH, Khan SA, et al.
    Heliyon, 2023 Feb;9(2):e13687.
    PMID: 36873152 DOI: 10.1016/j.heliyon.2023.e13687
    Perovskite materials play a vital role in the field of material science via experimental as well as theoretical calculations. Radium semiconductor materials are considered the backbone of medical fields. These materials are considered in high technological fields to be used as controlling the decay ability. In this study, radium-based cubic fluoro-perovskite XRaF3 (where X = Rb and Na) are calculated using a DFT (density functional theory). These compounds are cubic nature with 221 space groups that construct on CASTEP (Cambridge-serial-total-energy-package) software with ultra-soft PPPW (pseudo-potential plane-wave) and GGA (Generalized-Gradient-approximation)-PBE (Perdew-Burke-Ernzerhof) exchange-correlation functional. The structural, optical, electronic, and mechanical properties of the compounds are calculated. According to the structural properties, NaRaF3 and RbRaF3 have a direct bandgap with 3.10eV and 4.187eV of NaRaF3 and RbRaF3, respectively. Total density of states (DOS) and partial density of states (PDOS) provide confirmation to the degree of electrons localized in distinct bands. NaRaF3 material is semiconductors and RbRaF3 is insulator, according to electronic results. The imaginary element dispersion of the dielectric function reveals its wide variety of energy transparency. In both compounds, the optical transitions are examined by fitting the damping ratio for the notional dielectric function scaling to the appropriate peaks. The absorption and the conductivity of NaRaF3 compound is better than the RbRaF3 compound which make it suitable for the solar cell applications increasing the efficiency and work function. We observed that both compounds are mechanically stable with cubic structure. The criteria for the mechanical stability of compounds are also met by the estimated elastic results. These compounds have potential application in field of solar cell and medical.

    OBJECTIVES: The band gap, absorption and the conductivity are necessary conditions for potential applications. Here, literature was reviewed to check computational translational insight into the relationships between absorption and conductivity for solar cell and medical applications of novel RbRaF3 and NaRaF3 compounds.

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