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  1. Bajpai J, Pradhan A, Bajaj D, Verma AK, Kant S, Pandey AK, et al.
    Am J Cardiovasc Dis, 2023;13(1):1-9.
    PMID: 36938517
    Background Obstructive sleep apnea (OSA) is associated with many diseases, but evidence indicating that OSA is a risk factor for dyslipidemia is lacking. Aim This cross-sectional study investigated the prevalence of lipid abnormalities in patients with OSA and its association with OSA severity.

    MATERIAL AND METHODS: In this cross-sectional study, 102 patients with suspected OSA underwent standard polysomnography. All patients with an apnea-hypopnea index (AHI) of ≥5 with symptoms were diagnosed as having OSA. A fasting blood sample was collected from all patients. Blood levels of triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) were measured. The relationship between the AHI and lipid profiles was analyzed, and linear regression analysis was performed to evaluate the effect of dyslipidemia on OSA.

    RESULTS: The patients with OSA had a significantly higher TG level and a significantly lower HDL level than did those without OSA. The lipid abnormalities increased with OSA severity. The mean serum TG level was higher in the severe OSA group (175±46.5 vs. 153±42.45, mg/dl P = 0.048), and the mean serum HDL level was lower in the severe OSA group (38.43 ± 5.19 vs. 45.73 ± 4.98, mg/dl P = 0.004). Serum TG, cholesterol, and LDL levels were correlated with a BMI of <30 and a BMI of >30 in the OSA group. Linear regression analysis indicated that only age (β = 0.301, P = 0.000), BMI (β = 0.455, P = 0.000), serum HDL level (β = -0.297, P = 0.012), and serum LDL level (β = 0.429, P = 0.001) were the independent predictors of OSA.

    CONCLUSION: OSA and obesity are potential risk factors for dyslipidemia. The diagnosis of hyperlipidemia was linked to OSA, and the association was more significant with OSA severity. Hyperlipidemia was well recognized in patients with OSA. LDL and HDL are the independent predictors of OSA.

  2. Roney M, Dubey A, Hassan Nasir M, Tufail A, Tajuddin SN, Mohd Aluwi MFF, et al.
    J Biomol Struct Dyn, 2023 Sep 07.
    PMID: 37676262 DOI: 10.1080/07391102.2023.2252092
    Numerous malignancies, including breast cancer, non-small cell lung cancer, and chronic myeloid leukemia, are brought on by aberrant tyrosine kinase signaling. Since the current chemotherapeutic medicines are toxic, there is a great need and demand from cancer patients to find novel chemicals that are toxic-free or have low toxicity and that can kill tumor cells and stop their growth. This work describes the in-silico examination of substances from the drug bank as EGFR inhibitors. Firstly, drug-bank was screened using the pharmacophore technique to select the ligands and Erlotinib (DB00530) was used as matrix compound. The selected ligands were screened using ADMET and the hit compounds were subjected to docking. The lead compound from the docking was subjected to DFT and MD simulation study. Using the pharmacophore technique, 23 compounds were found through virtual drug bank screening. One hit molecule from the ADMET prediction was the subject of docking study. According to the findings, DB03365 molecule fits to the EGFR active site by several hydrogen bonding interactions with amino acids. Furthermore, DFT analysis revealed high reactivity for DB03365 compound in the binding pocket of the target protein, based on ELUMO, EHOMO and band energy gap. Furthermore, MD simulations for 100 ns revealed that the ligand interactions with the residues of EGFR protein were part of the essential residues for structural stability and functionality. However, DB03365 was a promising lead molecule that outperformed the reference compound in terms of performance and in-vitro and in-vivo experiments needs to validate the study.Communicated by Ramaswamy H. Sarma.
  3. Alhawarri MB, Al-Thiabat MG, Dubey A, Tufail A, Fouad D, Alrimawi BH, et al.
    RSC Adv, 2024 Mar 20;14(14):9878-9891.
    PMID: 38528929 DOI: 10.1039/d4ra01070a
    The current pharmacotherapies for Alzheimer's disease (AD) demonstrate limited efficacy and are associated with various side effects, highlighting the need for novel therapeutic agents. Natural products, particularly from medicinal plants, have emerged as a significant source of potential neuroprotective compounds. In this context, Cissampelos capensis L.f., renowned for its medicinal properties, has recently yielded three new proaporphine alkaloids; cissamaline, cissamanine, and cissamdine. Despite their promising bioactive profiles, the biological targets of these alkaloids in the context of AD have remained unexplored. This study undertakes a comprehensive in silico examination of the binding affinity and molecular interactions of these alkaloids with human protein targets implicated in AD. The drug likeness and ADME analyses indicate favorable pharmacokinetic profiles for these compounds, suggesting their potential efficacy in targeting the central nervous system. Molecular docking studies indicate that cissamaline, cissamanine, and cissamdine interact with key AD-associated proteins. These interactions are comparable to, or in some aspects slightly less potent than, those observed with established AD drugs, highlighting their potential as novel therapeutic agents for Alzheimer's disease. Crucially, Density Functional Theory (DFT) calculations offer deep insights into the electronic and energetic characteristics of these alkaloids. These calculations reveal distinct electronic properties, with differences in total energy, binding energy, HOMO-LUMO gaps, dipole moments, and electrophilicity indices. Such variations suggest unique reactivity profiles and molecular stability, pertinent to their pharmacological potential. Moreover, Molecular Electrostatic Potential (MEP) analyses provide visual representations of the electrostatic characteristics of these alkaloids. The analyses highlight areas prone to electrophilic and nucleophilic attacks, indicating their potential for specific biochemical interactions. This combination of DFT and MEP results elucidates the intricate electronic, energetic, and electrostatic properties of these compounds, underpinning their promise as AD therapeutic agents. The in silico findings of this study shed light on the promising potential of cissamaline, cissamanine, and cissamdine as agents for AD treatment. However, further in vitro and in vivo studies are necessary to validate these theoretical predictions and to understand the precise mechanisms through which these alkaloids may exert their therapeutic effects.
  4. Khan MWA, Das P, Bhavani V, Thakkar S, Nagella SP, Dubey A
    J Pharm Bioallied Sci, 2024 Feb;16(Suppl 1):S305-S307.
    PMID: 38595352 DOI: 10.4103/jpbs.jpbs_502_23
    INTRODUCTION: Although sevoflurane and desflurane have nearly identical blood-gas solubilities, current research suggests that airway reflexes recover more quickly with desflurane than sevoflurane; however, cognitive function recovery varies substantially. The current study was piloted to appraise the lengths of time needed to recover from anesthesia following desflurane and sevoflurane anesthesia.

    MATERIALS AND METHODS: A prospective clinical trial was piloted among 70 adult non-obese subjects who underwent elective surgery and were classified I-II by the "American Association of Anesthesiologists (ASA)". Sevoflurane and desflurane were tested among the subjects who were equally distributed. These agents were used in accordance with a normal general anaesthesia procedure. After they were extubated, tests for regaining cognitive function and airway reflexes were carried out, and different time intervals were recorded. The observations were calculated and P < 0.05 was used to conduct the statistical analysis.

    RESULTS: The average amount of time that passed between the patient's first vocal response and their first successful completion of the swallowing test was analogous between the two groups (T2) with 5.25 ± 3.11 vs 5.01 ± 2.12 in sevoflurane and desflurane, respectively. There was no significant variance at T2. For all the other time intervals of T1, T3, and T4, there was evidence of the significant variance.(P = 0.003; 0.0013; <0.001, respectively).

    CONCLUSION: Desflurane causes patients to recover more quickly than sevoflurane does after laparoscopic cholecystectomy under controlled circumstances.

  5. Shukla MK, Dubey A, Pandey S, Singh SK, Gupta G, Prasher P, et al.
    Curr Pharm Des, 2022;28(39):3202-3211.
    PMID: 35422206 DOI: 10.2174/1381612828666220413103831
    Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer.
  6. Kciuk M, Alam M, Ali N, Rashid S, Głowacka P, Sundaraj R, et al.
    Molecules, 2023 Jul 06;28(13).
    PMID: 37446908 DOI: 10.3390/molecules28135246
    Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.
  7. Roney M, Dubey A, Nasir MH, Huq AM, Tufail A, Tajuddin SN, et al.
    J Biomol Struct Dyn, 2023 Aug 26.
    PMID: 37632317 DOI: 10.1080/07391102.2023.2248262
    Aedes aegypti is the primary vector for the transmission of the dengue virus, which causes dengue fever, dengue hemorrhagic illness and dengue shock syndrome. There is now no antiviral medication available to treat DENV, which kills thousands of people each year and infects millions of individuals. A possible target for the creation of fresh and efficient dengue treatments is the DENV-3 NS5 MTase. So, Nigella sativa quinones were examined using in silico methods to find natural anti-DENV compounds. The in silico docking was conducted utilising the Discovery Studio software on the quinones of N. sativa and the active site of the target protein DENV-3 NS5 MTase. In addition, the druggability and pharmacokinetics of the lead compound were assessed. Dithymoquinone was comparable to the reference compound in terms of its ability to bind to the active site of target protein. Dithymoquinone met the requirements for drug likeness and Lipinski's principles, as demonstrated by the ADMET analysis and drug likeness results. The current study indicated that the dithymoquinone from N. sativa had anti-DENV activity, suggesting further drug development and dengue treatment optimisation.Communicated by Ramaswamy H. Sarma.
  8. Roney M, Dubey A, Issahaku AR, Uddin MN, Tufail A, Wilhelm A, et al.
    J Biomol Struct Dyn, 2024 Jan 23.
    PMID: 38260948 DOI: 10.1080/07391102.2024.2306197
    The goal of this work is to use a variety of in-silico techniques to identify anti-diabetic agents against DPP-IV enzyme from five main curcumin analogues. To produce the successful molecules, five main curcumin analogues were docked into the active site of DPP-IV enzyme. In comparison to the control molecule (Saxagliptin, -6.9 kcal/mol), all the compounds have the highest binding affinity (-7.6 to -7.7 kcal/mol) for the DPP-IV enzyme. These compounds underwent further testing for studies on drug-likeness, pharmacokinetics, and acute toxicity to see the efficacy and safety of compounds. To assess the stability of the docking complex and the binding posture identified during the docking experiment, our study got THC as the lead compound, which was then exposed to 200 ns of molecular dynamic simulation and PCA analysis. Additionally, DFT calculations were conducted to determine the thermodynamic, molecular orbital, and electrostatic potential characteristics of lead compound. Overall, the lead chemical has shown strong drug-like properties, is non-toxic, and has a sizable affinity for the DPP-IV enzyme.Communicated by Ramaswamy H. Sarma.
  9. Roney M, Huq AKMM, Issahaku AR, Soliman MES, Hossain MS, Mustafa AH, et al.
    J Biomol Struct Dyn, 2023;41(21):12186-12203.
    PMID: 36645141 DOI: 10.1080/07391102.2023.2166123
    Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research's primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex's stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate.Communicated by Ramaswamy H. Sarma.
  10. Huq AKMM, Roney M, Dubey A, Nasir MH, Tufail A, Aluwi MFFM, et al.
    PLoS One, 2024;19(3):e0299238.
    PMID: 38483871 DOI: 10.1371/journal.pone.0299238
    BACKGROUND: Currently, there is no antiviral medication for dengue, a potentially fatal tropical infectious illness spread by two mosquito species, Aedes aegypti and Aedes albopictus. The RdRp protease of dengue virus is a potential therapeutic target. This study focused on the in silico drug discovery of RdRp protease inhibitors.

    METHODS: To assess the potential inhibitory activity of 29 phenolic acids from Theobroma cacao L. against DENV3-NS5 RdRp, a range of computational methods were employed. These included docking, drug-likeness analysis, ADMET prediction, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. The aim of these studies was to confirm the stability of the ligand-protein complex and the binding pose identified during the docking experiment.

    RESULTS: Twenty-one compounds were found to have possible inhibitory activities against DENV according to the docking data, and they had a binding affinity of ≥-37.417 kcal/mol for DENV3- enzyme as compared to the reference compound panduratin A. Additionally, the drug-likeness investigation produced four hit compounds that were subjected to ADMET screening to obtain the lead compound, catechin. Based on ELUMO, EHOMO, and band energy gap, the DFT calculations showed strong electronegetivity, favouravle global softness and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups for catechin. The MD simulation result also demonstrated favourable RMSD, RMSF, SASA and H-bonds in at the binding pocket of DENV3-NS5 RdRp for catechin as compared to panduratin A.

    CONCLUSION: According to the present findings, catechin showed high binding affinity and sufficient drug-like properties with the appropriate ADMET profiles. Moreover, DFT and MD studies further supported the drug-like action of catechin as a potential therapeutic candidate. Therefore, further in vitro and in vivo research on cocoa and its phytochemical catechin should be taken into consideration to develop as a potential DENV inhibitor.

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