In-silico Codon Context and Synonymous Usage Analysis of Genes for Molecular Mechanisms Inducing Autophagy and Apoptosis with Reference to Neurodegenerative Disorders.

Background: Autophagy and apoptosis are cellular processes that maintain cellular homeostasis and remove damaged or aged organelles or aggregated and misfolded proteins. Stress factors initiate the signaling pathways common to autophagy and apoptosis. An imbalance in the autophagy and apoptosis, led by cascade of molecular mechanism prior to both processes culminate into neurodegeneration. Objective: In present study, we urge to investigate the codon usage pattern of genes which are common before initiating autophagy and apoptosis. Methods: In the present study, we took up eleven genes (DAPK1, BECN1, PIK3C3 (VPS34), BCL2, MAPK8, BNIP3 L (NIX), PMAIP1, BAD, BID, BBC3, MCL1) that are part of molecular signaling mechanism prior to autophagy and apoptosis. We analyzed dinucleotide odds ratio, codon bias, usage, context, and rare codon analysis. Results: CpC and GpG dinucleotides were abundant, with the dominance of G/C ending codons as preferred codons. Clustering analysis revealed that MAPK8 had a distinct codon usage pattern compared to other envisaged genes. Both positive and negative contexts were observed, and GAG-GAG followed by CTG-GCC was the most abundant codon pair. Of the six synonymous arginine codons, two codons CGT and CGA were the rarest. Conclusions: The information presented in the study may be used to manipulate the process of autophagy and apoptosis and to check the pathophysiology associated with their dysregulation.

A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds.

The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins.

A Comprehensive Review on Benzofuran Synthesis Featuring Innovative and Catalytic Strategies.

Benzofurans have intrigued both pharmaceutical researchers and chemists owing to the medicinal usage of their derivatives against copious disease-causing agents (i.e., bacteria, viruses, and tumors). These heterocyclic scaffolds are pervasively encountered in a number of natural products and drugs. The ever-increasing utilization of benzofuran derivatives as pharmaceutical agents persuaded the chemists to devise novel and facile methodological approaches to assemble the biologically potent benzofuran nucleus. This review summarizes the current developments regarding the innovative synthetic routes and catalytic strategies to procure the synthesis of benzofuran heterocycles with their corresponding mechanistic details, reported by several research groups during 2021-2023.

α-Glucosidase inhibitory potential of Oroxylum indicum using molecular docking, molecular dynamics, and in vitro evaluation.

Background: According to the International Diabetes Federation, there will be 578 million individuals worldwide with diabetes by 2030 and 700 million by 2045. One of the promising drug targets to fight diabetes is α-glucosidase (AG), and its inhibitors may be used to manage diabetes by reducing the breakdown of complex carbohydrates into simple sugars. The study aims to identify and validate potential AG inhibitors in natural sources to combat diabetes. Methods: Computational techniques such as structure-based virtual screening and molecular dyncamic simulation were employed to predict potential AG inhibitors from compounds of Oroxylum indicum. Finally, in silico results were validated by in vitro analysis using n-butanol fraction of crude methanol extracts. Results: The XP glide scores of top seven hits OI_13, OI_66, OI_16, OI_44, OI_43, OI_20, OI_78 and acarbose were -14.261, -13.475, -13.074, -13.045, -12.978, -12.659, -12.354 and -12.296 kcal/mol, respectively. These hits demonstrated excellent binding affinity towards AG, surpassing the known AG inhibitor acarbose. The MM-GBSA dG binding energies of OI_13, OI_66, and acarbose were -69.093, -62.950, and -53.055 kcal/mol, respectively. Most of the top hits were glycosides, indicating that active compounds lie in the n-butanol fraction of the extract. The IC50 value for AG inhibition by n-butanol fraction was 248.1 µg/ml, and for that of pure acarbose it was 89.16 µg/ml. The predicted oral absorption rate in humans for the top seven hits was low like acarbose, which favors the use of these compounds as anti-diabetes in the small intestine. Conclusion: In summary, the study provides promising insights into the use of natural compounds derived from O. indicum as potential AG inhibitors to manage diabetes. However, further research, including clinical trials and pharmacological studies, would be necessary to validate their efficacy and safety before clinical use.

Gaining exposure on perceptions of sunscreen: a national survey of melanoma patients.

Melanoma incidence is increasing. We ascertained perceptions regarding sunscreen and factors influencing choice in patients with melanoma. A survey was distributed to all the supporters of a melanoma patient support group. 571 responses were received across six weeks. Most (79.2%; n=452) indicated they knew how much sunscreen to apply; the most popular frequency of application was once daily (32%, n=180). The most popular cosmetic benefit respondents indicated was reduced redness on sun-exposed areas of skin (73.2%; n=418). Most (96.7%; n=552) agreed more education is needed regarding importance of wearing sunscreen. The three most popular factors in influencing sunscreen choice were SPF more than 50 (n=299; 52.4%), recommendation by a dermatologist (n=267; 46.8%) and price (n=262; 45.9%). Sustainable package design (n=45; 7.9%) and ethical sourcing of ingredients (n=65; 11.4%) were not ranked highly. Given 42% (n=240) only applied sunscreen during sunshine, an education campaign is required. Industry should consider public education regarding sustainability. A further study ascertaining views and perceptions of sunscreen in the non-melanoma cohort is strongly encouraged.

Green Biocatalyst for Ultrasound-Assisted Thiazole Derivatives: Synthesis, Antibacterial Evaluation, and Docking Analysis.

The catalytic activity of chitosan (Cs) and grafted Cs led to the preparation of terephthalohydrazide Cs Schiff's base hydrogel (TCsSB), which was then investigated as an eco-friendly biocatalyst for synthesizing novel thiazole derivatives. TCsSB exhibited greater surface area and higher thermal stability compared to Cs, making it a promising eco-friendly biocatalyst. We synthesized two novel series of thiazoles via the reaction of 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothioamide with various hydrazonoyl chlorides and 2-bromo-1-arylethan-1-ones, employing ultrasonic irradiation and using TCsSB as a catalyst. A comparative study between Cs and TCsSB revealed higher yields than TCsSB. The methodology offered advantages such as mild reaction conditions, quick reaction times, and high yields. TCsSB could be reused multiple times without a significant loss of potency. The chemical structures of the newly synthesized compounds were verified through IR, 1H NMR, 13C NMR, and MS analyses. Six synthesized compounds were assessed for their in vitro antibacterial effectiveness by establishing the minimum inhibitory concentration against four distinct bacterial strains. The docking analyses revealed favorable binding scores against several amino acids within the selected protein (PDB Code-1MBT) for these compounds, with compound 4c exhibiting particularly noteworthy binding properties. Additionally, the in silico ADME parameter estimation for all compounds indicated favorable pharmacological properties for these compounds.

Copper-based metal-organic frameworks (BDC-Cu MOFs) as supporters for α-amylase: Stability, reusability, and antioxidant potential.

Copper-based metal-organic frameworks (BDC-Cu MOFs) were synthesized via a casting approach using 1,4-benzene dicarboxylic (BDC) as organic ligand and their properties characterized. The obtained materials were then utilized to immobilize the α-amylase enzyme. The chemical composition and functional components of the synthesized support (BDC-Cu MOFs) were investigated with Fourier transform infrared spectroscopy (FTIR), the surface morphology was determined with scanning electron microscopy (SEM), and the elemental composition was established with energy dispersive X-ray (EDX) analyses. X-ray diffraction (XRD) was employed to analyze the crystallinity of the synthesized DBC-Cu MOFs. The zeta potentials of DBC-Cu MOFs and DBC-Cu MOFs@α-amylase were determined. The immobilized α-amylase demonstrated improved catalytic activity and reusability compared to the free form. Covalent attachment of the α-amylase to BDC-Cu provided an immobilization yield (IY%) of 81% and an activity yield (AY%) of 89%. The immobilized α-amylase showed high catalytic activity and 81% retention even after ten cycles. Storage at 4 °C for eight weeks resulted in a 78% activity retention rate for DBC-Cu MOFs@α-amylase and 49% retention for the free α-amylase. The optimum activity occurred at 60 °C for the immobilized form, whereas the free form showed optimal activity at 50 °C. The free and immobilized α-amylase demonstrated peak catalytic activities at pH 6.0. The maximum reaction velocities (Vmax) values were 0.61 U/mg of protein for free α-amylase and 0.37 U/mg of protein for BDC-Cu MOFs@α-amylase, while the Michaelis‒Menten affinity constants (Km) value was lower for the immobilized form (5.46 mM) than for the free form (11.67 mM). Treatments of maize flour and finger millet samples with free and immobilized α-amylase resulted in increased total phenolic contents. The enhanced antioxidant activities of the treated samples were demonstrated with decreased IC50 values in ABTS and DPPH assays. Overall, immobilization of α-amylase on BDC-Cu MOFs provided improved stability and catalytic activity and enhanced the antioxidant potentials of maize flour and finger millet.

New enantioenriched ß-indolyl ketones as aromatase inhibitors: Unraveling heme-ligand interactions by MD simulation and MMPBSA analysis.

A series of enantioenriched ß-indolyl ketones as aromatase inhibitors (AI) is synthesized through the Michael-type Friedel-Crafts alkylation of indole. A highly efficient bifunctionalized amino catalyst is developed to access structurally diverse ß-indolyl ketones in high yields (up to 91%) and excellent enantioselectivity (enantiomeric ratio up to 98:2). All the synthesized compounds demonstrated promising aromatase inhibitory potential, where ortho-substituted analogs (3c and 3e) were found most active with IC50 values of 0.68 and 0.90 µM, respectively. Both of these compounds exhibited significant cytotoxicity (IC50 = 0.34 and 0.37 µM) against the MCF-7 breast cancer cell line in the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Molecular docking studies of the synthesized compounds demonstrate favorable binding interactions with the estrogens controlling CYP19A1 (3EQM) and metabolizing CYP3A4 (5VCC) enzymes. Molecular dynamic (MD) simulation analysis revealed the essentiality of heme-ligand interactions to build a stable protein-ligand complex. An average root mean square deviation of 0.35 nm observed during a 100-ns MD simulation and binding free energy in the range of -190 to -227 kJ/mol calculated by g_mmpbsa analysis authenticated the stability of the 3c-3EQM complex. ADMET and drug-likeness parameters supported the suitability of these indole derivatives as the drug lead to develop potent inhibitors for estrogen-dependent breast cancer.

A systematic review and meta-analysis of oncological outcomes with transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal (taTME) excision is a method used to assist in the radical removal of the rectum. By adopting the concept of natural orifice surgery, it offers potential benefits over conventional techniques. Early enthusiasm for this strategy led to its rapid and widespread adoption. The imposing of a local moratorium was precipitated by the discovery in Norway of an uncommon multifocal pattern of locoregional recurrence. The aim of this systematic review and meta-analysis was to determine the incidence of local recurrence after taTME for rectal cancer. METHOD: Conforming to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines checklist, a systematic review and meta-analysis was conducted. This included case series and comparative studies between taTME and preferentially laparoscopic procedures published between 2010 and 2021. RESULTS: There were a total of 1175 studies retrieved. After removal and screening for quality and relevance, the final analysis contained 40 studies. The local recurrence rate following taTME was 3.4% (95% CI 2.9%-3.9%, I2 = 0%) in 4987 patients with follow-up durations ranging from 0.7 to 5.5 years. Compared with laparoscopic TME, local recurrence was not statistically different for the taTME group (p = 0.076); however, it was less probable (OR = 0.51, 95% CI 0.24-1.09, I2 = 0%). Systemic recurrence and circumferential resection margin status were secondary outcomes; however, the differences were not statistically significant. CONCLUSION: Our data suggest that the local recurrence for regular laparoscopic and transanal TME surgeries may be comparable, suggesting that taTME can be performed without influencing locoregional oncological outcomes in patients treated at specialized institutions and who have been cautiously selected.

Estrogen Receptor Alpha Binders for Hormone-Dependent Forms of Breast Cancer: e-QSAR and Molecular Docking Supported by X-ray Resolved Structures.

Cancer, a life-disturbing and lethal disease with a high global impact, causes significant economic, social, and health challenges. Breast cancer refers to the abnormal growth of cells originating from breast tissues. Hormone-dependent forms of breast cancer, such as those influenced by estrogen, prompt the exploration of estrogen receptors as targets for potential therapeutic interventions. In this study, we conducted e-QSAR molecular docking and molecular dynamics analyses on a diverse set of inhibitors targeting estrogen receptor alpha (ER-α). The e-QSAR model is based on a genetic algorithm combined with multilinear regression analysis. The newly developed model possesses a balance between predictive accuracy and mechanistic insights adhering to the OECD guidelines. The e-QSAR model pointed out that sp2-hybridized carbon and nitrogen atoms are important atoms governing binding profiles. In addition, a specific combination of H-bond donors and acceptors with carbon, nitrogen, and ring sulfur atoms also plays a crucial role. The results are supported by molecular docking, MD simulations, and X-ray-resolved structures. The novel results could be useful for future drug development for ER-α.

Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation.

4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4H-chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b, suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations.

Acute Rheumatic Fever in Children: The Known and the Unknown Among Saudi Mothers in the Jazan Region.

Background Acute rheumatic fever (ARF) is a significant public health problem that causes morbidity and mortality in low and middle-income countries. Therefore, this study aims to assess mothers' knowledge of acute rheumatic fever and their attitudes in the Jazan region. Methods A cross-sectional study was conducted between the mothers using an online survey. The knowledge level was ranked as poor, fair, and good. In contrast, the attitudes were ranked as positive or negative. Association with sociodemographic variables was assessed, and statistical significance was set at p < 0.05. Results Four hundred thirty-six (436) mothers were included; 39.9% of them were aged 21-30 years, 68.8% were married, 57.3% were non-workers, and 72.2% were university-educated. Most of the mothers had a poor level of knowledge (53%); however, positive attitudes toward the disease were reported in 79.1% of mothers. The poor knowledge levels were related to age, marital status, occupation, and monthly income. Conclusion Despite having positive attitudes toward diagnosing and managing ARF, most of the mothers showed poor knowledge of acute rheumatic fever. This study highlights the situation in the Jazan region, which could be an essential basis for constructing an educational program to raise awareness and knowledge of acute rheumatic fever in the community.

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (-7.55 kcal/mol) with the active site of serine protease, better than compound 4c (-6.90 kcal/mol) as well as indole-based control compound 5 (-7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 µg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 µg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 µg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 µg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

Sandalwood Oils of Different Origins Are Active In Vitro against Madurella mycetomatis, the Major Fungal Pathogen Responsible for Eumycetoma.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as "sandalwood oils". Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-ß-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the ß-isomer.

Using a Disposable Flexible Fiberoptic Scope as a Bougie for Difficult Intubation.

In this case report, we describe two difficult intubations in which an endotracheal tube was threaded over a fiberoptic bronchoscope that was acting as a bougie. Our patients initially presented with limited neck extension, narrow mouth opening, and restricted view of the glottic region. A fiberoptic bronchoscope was guided through while the patient was oxygenated through a laryngeal mask. After the scope provided an unrestricted view of the vocal cords, the digital module was removed by cutting the fiberoptic thread, and an endotracheal tube was passed through. After proper confirmation of the endotracheal tube position, the intubation was deemed successful and thereby, we share our experience with the novel technique. This technique may potentially improve critical patient outcomes whether in trauma or an unexpectedly difficult intubation.

Patient perspectives on ionising radiation exposure from computed tomography in Saudi Arabia: a knowledge and perception study.

The objective of this study was to evaluate patient knowledge and understanding of ionising radiation and dosage, as well as the accompanying risks related to computed tomography scans. A total of 412 outpatients who underwent computed tomography (CT) scans were surveyed to assess their understanding of radiation dose and exposure risks. CT was correctly classified as an ionising radiation by 56.8% of the respondents. More than half of the patients reported that a CT scan increases the probability of inducing cancer. Awareness of varying radiation doses in different CT exams was noted in 75.2% of patients, but only 21.4% reported having discussions with their physician about radiation dose. Gender, age and employment were significantly correlated with knowledge levels. The survey findings indicate a limited understanding of the hazards associated with ionising radiation used in CT scans, highlighting a need for increased awareness and education on radiation protection to ensure informed consent.

The Saudi initiative for asthma - 2024 update: Guidelines for the diagnosis and management of asthma in adults and children.

The Saudi Initiative for Asthma 2024 (SINA-2024) is the sixth version of asthma guidelines for the diagnosis and management of asthma for adults and children that was developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up-to-date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA Panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5-12 years, and children aged <5 years. SINA guidelines have focused more on personalized approaches reflecting a better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. The medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient-doctor partnership in the management that also includes a self-management plan.

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors.

Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of -8.0 (5b) and -8.1 (7e) kcal/mol. The binding energy of thiourea was -2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and -6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.