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This international cross-sectional survey examined the potential role of organizational psychological support in mitigating the association between experiencing social discrimination against long-term care (LTC) facilities' healthcare professionals (HCPs) and their intention to stay in the current workplace during the COVID-19 pandemic. Participants included a convenience sample of 2,143 HCPs (nurses [21.5 %], nurse aids or residential care workers [40.1 %], social workers [12.1 %], and others [26.4 %]) working at 223 LTC facilities in 13 countries/regions. About 37.5 % of the participants reported experiencing social discrimination, and the percentage ranged from 15.3 % to 77.9 % across countries/regions. Controlling for socio-demographic and work-related variables, experiencing social discrimination was significantly associated with a lower intention to stay, whereas receiving psychological support showed a statistically significant positive association (p-value=0.015 and <0.001, respectively). The interaction term between social discrimination and psychological support showed a statistically significant positive association with the intention to stay, indicating a moderating role of the psychological support.
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Substituting sugar with noncaloric sweeteners prevents overweight and diabetes development. They come in two types: artificial, like aspartame and sucralose, and natural, such as sorbitol. This research aimed to assess the effects of sucrose and these sweeteners on nutritional parameters, hematological parameters, hormones, and anti- and pro-inflammatory cytokines in male rats. Thirty rats had been separated into five groups. The results showed the highest significant increase in body weight gain, total food intake, and feed efficiency noticed in the aspartame group followed by sucralose, sucrose, and sorbitol, respectively. In contrast to RBCs and platelets, all sweeteners significantly reduced the hemoglobin level, Hct %, and WBC count. The aspartame group showed the highest decline in glycoproteins, steroids, and T3, and T4 hormones and a dramatic elevation in thyroid stimulating hormone, eicosanoid, and amine hormones compared with the control group. A vigorous elevation in anti- and proinflammatory cytokine levels was observed in the aspartame group, followed by sucralose, sucrose, and sorbitol groups. Aspartame has the highest docking scores when studying the interactions of sweeteners and a target protein associated with hormones or cytokines using in silico molecular docking, with the best absorption, distribution, metabolism, elimination, and toxicity properties compared to the remaining sweeteners.
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Pyrazole heterocycle is regarded as an extremely significant agent for the therapy of inflammation. Celecoxib, lonazolac, deracoxib, and phenylbutazone are examples of commercially approved pyrazole drugs with COX-2 inhibitory potential for curing inflammation. There have been recently many reviews for the biological significance of pyrazole derivatives. This review talks about pyrazole derivatives with anti-inflammatory activity and also sheds the light on the recent updates on pyrazole research with an emphasis on some synthetic pathways utilized to construct this privileged scaffold and structure activity relationship that accounts for the anti-inflammatory activity in an attempt to pave the opportunity for medicinal chemists to develop novel anti-inflammatory agents with better COX-2 selectivity.
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In this study, we delve into the intricacies of elastoviscoplastic (EVP) fluids, particularly focusing on how polymer additives influence their extensional behavior. Our findings reveal that polymer additives significantly alter the extensional properties of the EVP fluids, such as relaxation time and extensional stresses while having negligible impact on the shear rheology. Interestingly, the modified fluids exhibit a transition from yield stress-like behavior to viscoelastic-like behavior under high extensional rates, ultimately leading to destabilization under extreme deformation. This research enhances the fundamental understanding of EVP fluids and highlights potential advancements in applications, especially in precision-demanding fields like 3D printing.
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Quinazoline and quinazolinone derivatives piqued medicinal chemistry interest in developing novel drug candidates owing to their pharmacological potential. They are important chemicals for the synthesis of a variety of physiologically significant and pharmacologically useful molecules. Quinazoline and quinazolinone derivatives have anticancer, anti-inflammatory, antidiabetic, anticonvulsant, antiviral, and antimicrobial potential. The increased understanding of quinazoline and quinazolinone derivatives in biological activities provides opportunities for new medicinal products. The present review focuses on novel advances in the synthesis of these important scaffolds and other medicinal aspects involving drug design, structure-activity relationship, and action mechanisms of quinazoline and quinazolinone derivatives to help in the development of new quinazoline and quinazolinone derivatives.
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Simulação de Acoplamento Molecular , Quinazolinas , Quinazolinonas , Quinazolinas/farmacologia , Quinazolinas/síntese química , Quinazolinas/química , Quinazolinonas/farmacologia , Quinazolinonas/síntese química , Quinazolinonas/química , Humanos , Relação Estrutura-Atividade , Desenho de Fármacos , Animais , Estrutura MolecularRESUMO
BACKGROUND: This study aimed to investigate the alterations in biochemical and physiological responses of oat plants exposed to antimony (Sb) contamination in soil. Specifically, we evaluated the effectiveness of an arbuscular mycorrhizal fungus (AMF) and olive mill waste (OMW) in mitigating the effects of Sb contamination. The soil was treated with a commercial strain of AMF (Rhizophagus irregularis) and OMW (4% w/w) under two different levels of Sb (0 and 1500 mg kg-1 soil). RESULTS: The combined treatment (OMW + AMF) enhanced the photosynthetic rate (+ 40%) and chlorophyll a (+ 91%) and chlorophyll b (+ 50%) content under Sb condition, which in turn induced more biomass production (+ 67-78%) compared to the contaminated control plants. More photosynthesis in OMW + AMF-treated plants gives a route for phenylalanine amino acid synthesis (+ 69%), which is used as a precursor for the biosynthesis of secondary metabolites, including flavonoids (+ 110%), polyphenols (+ 26%), and anthocyanins (+ 63%) compared to control plants. More activation of phenylalanine ammonia-lyase (+ 38%) and chalcone synthase (+ 26%) enzymes in OMW + AMF-treated plants under Sb stress indicated the activation of phenylpropanoid pathways in antioxidant metabolites biosynthesis. There was also improved shifting of antioxidant enzyme activities in the ASC/GSH and catalytic pathways in plants in response to OMW + AMF and Sb contamination, remarkably reducing oxidative damage markers. CONCLUSIONS: While individual applications of OMW and AMF also demonstrated some degree of plant tolerance induction, the combined presence of AMF with OMW supplementation significantly enhanced plant biomass production and adaptability to oxidative stress induced by soil Sb contamination.
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Antimônio , Micorrizas , Olea , Poluentes do Solo , Micorrizas/fisiologia , Olea/microbiologia , Poluentes do Solo/metabolismo , Antimônio/metabolismo , Adaptação Fisiológica , Resíduos Industriais , Fotossíntese/efeitos dos fármacos , Biodegradação Ambiental , BiomassaRESUMO
Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives have been previously confirmed as antibacterial. In this investigation, biological screening and molecular docking studies were performed for derivatives 1-15, with compounds 2, 7, 8, 14 and 15 yielding the best energy scores (from -20.7986 to -10.5302 kcal/mol). Drug-likeness and in silico ADME prediction for the most potent derivatives, 2, 7, 8, 14 and 15, were predicted (from 84.46 to 96.85%). The latter compounds showed good recorded physicochemical properties and pharmacokinetics. Compound 8 demonstrated the strongest inhibition, which was similar to the positive control (eflornithine) against Trypanosoma brucei brucei (WT), with an EC50 of 25.12 and 22.52µM, respectively. Moreover, compound 14 exhibited the best activity against Leishmania mexicana promastigotes and Leishmania major promastigotes (EC50 =46.85; 40.78µM, respectively).
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Simulação de Acoplamento Molecular , Pirazóis , Pirimidinas , Tripanossomicidas , Trypanosoma brucei brucei , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Trypanosoma brucei brucei/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/química , Tripanossomicidas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/síntese química , Leishmania mexicana/efeitos dos fármacos , Leishmania major/efeitos dos fármacos , Antiprotozoários/farmacologia , Antiprotozoários/química , Simulação por Computador , Compostos Azo/farmacologia , Compostos Azo/química , Compostos Azo/síntese química , Relação Estrutura-Atividade , Testes de Sensibilidade ParasitáriaRESUMO
Liposomes are spherical vesicles formed from bilayer lipid membranes that are extensively used in targeted drug delivery as nanocarriers to deliver therapeutic reagents to specific tissues and organs in the body. Recently, we have reported using estrone as an endogenous ligand on doxorubicin-encapsulating liposomes to target estrogen receptor (ER)-positive breast cancer cells. Estrone liposomes were synthesized using the thin-film hydration method, which is a long, arduous, and multistep process. Here, we report using a herringbone micromixer to synthesize estrone liposomes in a simple and rapid manner. A solvent stream containing the lipids was mixed with a stream of phosphate buffer saline (PBS) inside a microchannel integrated with herringbone-shaped ridges that enhanced the mixing of the two streams. The small scale involved enabled rapid solvent exchange and initiated the self-assembly of the lipids to form the required liposomes. The effect of different parameters on liposome size, such as the ratio between the flow rate of the solvent and the buffer solutions (FRR), total flow rate, lipid concentrations, and solvent type, were investigated. Using this commercially available chip, we obtained liposomes with a radius of 66.1 ± 11.2 nm (mean ± standard deviation) and a polydispersity of 22% in less than 15 minutes compared to a total of â¼ 11 hours using conventional techniques. Calcein was encapsulated inside the prepared liposomes as a model drug and was released by applying ultrasound at different powers. The size of the prepared liposomes was stable over a period of one month. Overall, using microfluidics to synthesize estrone liposomes simplified the procedure considerably and improved the reproducibility of the resulting liposomes.
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Estrona , Lipossomos , Lipossomos/química , Estrona/química , Humanos , Desenho de Equipamento , Técnicas Analíticas Microfluídicas/métodos , Técnicas Analíticas Microfluídicas/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/administração & dosagemRESUMO
BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Pericitos , Células Endoteliais/metabolismo , Tecido Adiposo/metabolismo , Apoptose , Células CultivadasRESUMO
Monoamine oxidases (MAOs), specifically MAO-A and MAO-B, play important roles in the breakdown of monoamine neurotransmitters. Therefore, MAO inhibitors are crucial for treating various neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). In this study, we developed a novel cheminformatics pipeline by generating three diverse molecular feature-based machine learning-assisted quantitative structural activity relationship (ML-QSAR) models concerning MAO-B inhibition. PubChem fingerprints, substructure fingerprints, and one-dimensional (1D) and two-dimensional (2D) molecular descriptors were implemented to unravel the structural insights responsible for decoding the origin of MAO-B inhibition in 249 non-reductant molecules. Based on a random forest ML algorithm, the final PubChem fingerprint, substructure fingerprint, and 1D and 2D molecular descriptor prediction models demonstrated significant robustness, with correlation coefficients of 0.9863, 0.9796, and 0.9852, respectively. The significant features of each predictive model responsible for MAO-B inhibition were extracted using a comprehensive variance importance plot (VIP) and correlation matrix analysis. The final predictive models were further developed as a web application, MAO-B-pred ( https://mao-b-pred.streamlit.app/ ), to allow users to predict the bioactivity of molecules against MAO-B. Molecular docking and dynamics studies were conducted to gain insight into the atomic-level molecular interactions between the ligand-receptor complexes. These findings were compared with the structural features obtained from the ML-QSAR models, which supported the mechanistic understanding of the binding phenomena. The presented models have the potential to serve as tools for identifying crucial molecular characteristics for the rational design of MAO-B target inhibitors, which may be used to develop effective drugs for neurodegenerative disorders.
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Aplicativos Móveis , Doenças Neurodegenerativas , Humanos , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Doenças Neurodegenerativas/tratamento farmacológico , Dopaminérgicos/farmacologia , Internet , Relação Estrutura-AtividadeRESUMO
BACKGROUND Cases involving penetrating abdominal trauma may be complex and often involve damage to multiple organ systems. Synthetic, biologic, and reinforced biologic matrices/reinforced tissue matrices (RBMs/RTMs) are frequently used in hernia repair and other surgical procedures requiring reinforcement, including trauma cases that require abdominal repair. CASE REPORT The first case was a 35-year-old male patient with a stab wound (SW) to the right side of the chest and the abdomen resulting in damage to the diaphragm, epicardium, liver, and duodenum. The second case was a 22-year-old male patient who suffered multiple traumas after an automated trencher accident, including a skull fracture with exposed brain and major lacerations to the shoulder and abdomen causing a large right-flank hernia. In both cases, OviTex® (TELA Bio, Inc., Malvern, PA), a reinforced tissue matrix (RTM), was used to help obtain and maintain abdominal wall closure. We also present an institutional economic analysis using data from the author's institution with average case cost and future projections for procedure volume and product usage volume through 2021. CONCLUSIONS We report favorable outcomes in a series of patients with contaminated (CDC Wound Class III) surgical fields who underwent abdominal wall closure and reinforcement with OviTex RTM. Our work adds to the growing body of literature suggesting that reinforced biologics offer a potential alternative to biological meshes in the setting of a contaminated surgical field. Additionally, in comparison to other commonly available biologic matrices, use of OviTex RTM may be a cost-effective option to achieve abdominal wall closure even in complex cases.
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Traumatismos Abdominais , Parede Abdominal , Hérnia Ventral , Masculino , Humanos , Ovinos , Animais , Adulto , Adulto Jovem , Parede Abdominal/cirurgia , Herniorrafia/métodos , Traumatismos Abdominais/cirurgia , Fígado/cirurgia , Próteses e Implantes , Telas Cirúrgicas , Hérnia Ventral/cirurgiaRESUMO
BACKGROUND: Stress and conflict in emergency departments are inevitable but can be managed. A supportive work environment is key to helping emergency care providers, especially nurses, constructively manage work-related stress and conflict. AIM: The aim of this study was to assess the influence of supportive work environments on work-related stress and conflict management style among emergency care nurses. METHODS: A descriptive correlational research design was utilized. Data were collected from 221 staff nurses recruited from two university hospital emergency departments in Alexandria, Egypt. Three instruments were used: (1) perceived organizational support scale, (2) nurses' occupational stressors scale, and (3) conflict management style inventory. RESULTS: There was a highly significant correlation between supportive work environments and work-related stress (p = .000) and a significant correlation between supportive work environments and conflict management style (p = .026). Supportive work environments had a significant inverse negative relationship with work-related stress experienced by nurses (p = .001) and accounted for 51% of variance in work-related stress. Meanwhile, supportive work environments had a significant positive relationship with conflict management styles of nurses (p = .026). Work-related stress had a significant relationship with nurses' conflict management style (p = .000) and accounted for 45% of the variance in conflict management style. LINKING EVIDENCE TO ACTION: The style of conflict management modeled by staff within emergency departments can positively or negatively influence the work environment and level of work-related stress. There is a necessity to cultivate a supportive culture for nurses in emergency departments to develop skills for constructive conflict management styles to reduce work-related stress.
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Serviços Médicos de Emergência , Recursos Humanos de Enfermagem Hospitalar , Estresse Ocupacional , Humanos , Conflito Psicológico , Condições de Trabalho , Inquéritos e QuestionáriosRESUMO
To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.
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[This corrects the article DOI: 10.1039/D3RA07035B.].
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Almost a billion people worldwide suffer from neurological disorders, which pose public health challenges. An important enzyme that is well-known for many neurodegenerative illnesses is monoamine oxidase (MAO). Although several promising drugs for the treatment of MAO inhibition have recently been examined, it is still necessary to identify the precise structural requirements for robust efficacy. Atom-based, field-based, and GA-MLR (genetic algorithm multiple linear regression) models were created for this investigation. All of the models have strong statistical (R2 and Q2) foundations because of both internal and external validation. Our dataset's molecule has a higher docking score than safinamide, a well-known and co-crystallized MAO-B inhibitor, as we also noticed. Using the SwissSimilarity platform, we further inquired which of our docked molecules would be the best for screening. We chose ZINC000016952895 as the screen molecule with the best binding docking score (XP score = -13.3613). Finally, the 100 ns for the ZINC000016952895-MAO-B complex in our MD investigations is stable. For compounds that we hit, also anticipate ADME properties. Our research revealed that the successful compound ZINC000016952895 might pave the way for the future development of MAO inhibitors for the treatment of neurological disease.Communicated by Ramaswamy H. Sarma.
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Isatina , Doenças Neurodegenerativas , Humanos , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/metabolismo , Relação Quantitativa Estrutura-Atividade , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Monoaminoxidase/química , Doenças Neurodegenerativas/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
AIMS: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. DESIGN: Cross-sectional survey. METHODS: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. RESULTS: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance. CONCLUSIONS: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. IMPACT: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Assistência de Longa Duração , Estudos Transversais , Pandemias/prevenção & controle , Hong Kong/epidemiologiaRESUMO
Click chemistry is a set of easy, atom-economical reactions that are often utilized to combine two desired chemical entities. Click chemistry accelerates lead identification and optimization, reduces the complexity of chemical synthesis, and delivers extremely high yields without undesirable byproducts. The most well-known click chemistry reaction is the 1,3-dipolar cycloaddition of azides and alkynes to form 1,2,3-triazoles. The resulting 1,2,3-triazoles can serve as both bioisosteres and linkers, leading to an increase in their use in the field of drug discovery. The current Review focuses on the use of click chemistry to identify new molecules for treating neurodegenerative diseases and in other areas such as peptide targeting and the quantification of biomolecules.
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Eighteen isatin-based benzyloxybenzaldehyde derivatives from three subseries, ISB, ISFB, and ISBB, were synthesized and their ability to inhibit monoamine oxidase (MAO) was evaluated. The inhibitory activity of all synthesized compounds was found to be more profound against MAO-B than MAO-A. Compound ISB1 most potently inhibited MAO-B with an IC50 of 0.124 ± 0.007 µM, ensued by ISFB1 (IC50 = 0.135 ± 0.002 µM). Compound ISFB1 most potently inhibited MAO-A with an IC50 of 0.678 ± 0.006 µM, ensued by ISBB3 (IC50 = 0.731 ± 0.028 µM), and had the highest selectivity index (SI) value (55.03). The three sub-parental compounds, ISB1, ISFB1, and ISBB1, had higher MAO-B inhibition than the other derivatives, indicating that the substitutions of the 5-H in the A-ring of isatin diminished the inhibition of MAO-A and MAO-B. Among these, ISB1 (para-benzyloxy group in the B-ring) displayed more significant MAO-B inhibition when compared to ISBB1 (meta-benzyloxy group in the B-ring). ISB1 and ISFB1 were identified to be competitive and reversible MAO-B inhibitors, having Ki values of 0.055 ± 0.010, and 0.069 ± 0.025 µM, respectively. Furthermore, in the parallel artificial membrane penetration assay, ISB1 and ISFB1 traversed the blood-brain barrier in the in vitro condition. Additionally, the current study found that ISB1 decreased rotenone-induced cell death in SH-SY5Y neuroblastoma cells. In docking and simulation studies, the hydrogen bonding formed by the imino nitrogen in ISB1 and the pi-pi stacking interaction of the phenyl ring in isatin significantly aided in the protein-ligand complex's stability, effectively inhibiting MAO-B. According to these observations, the MAO-B inhibitors ISB1 and ISFB1 were potent, selective, and reversible, making them conceivable therapies for neurological diseases.
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Tuberculosis is one of the most ancient infectious diseases known to mankind predating upper Paleolithic era. In the current scenario, treatment of drug resistance tuberculosis is the major challenge as the treatment options are limited, less efficient and more toxic. In our study we have developed an atom based 3D QSAR model, statistically validated sound with R2 > 0.90 and Q2 > 0.72 using reported direct inhibitors of InhA (2018-2022), validated by enzyme inhibition assay. The model was used to screen a library of 3958 molecules taken from Binding DB and candidates molecules with promising predicted activity value (pIC50) > 5) were selected for further analyzed screening by using molecular docking, ADME profiling and molecular dynamic simulations. The lead molecule, ZINC11536150 exhibited good docking score (glideXP = -11.634 kcal/mol) compared to standard triclosan (glideXP = -7.129 kcal/mol kcal/mol) and through molecular dynamics study it was observed that the 2nv6-complex of ZINC11536150 with Mycobacterium tuberculosis InhA (PDB entry: 2NV6) complex remained stable throughout the entire simulation time of 100 ns.Communicated by Ramaswamy H. Sarma.