Anti-Infective Agents最新文献

{"title":"Hierarchical Virtual Screening of SARS-CoV-2 Main Protease Potential Inhibitors: Similarity Search, Pharmacophore Modeling, and Molecular\u0000Docking Study","authors":"H. Mando, Iyad allous","doi":"10.2174/0122113525280410240106122715","DOIUrl":"https://doi.org/10.2174/0122113525280410240106122715","url":null,"abstract":"\u0000\u0000The outbreak of COVID-19 caused by severe acute respiratory syndrome\u0000coronavirus2 (SARS-CoV-2) resulted in a widespread pandemic. Various approaches involved\u0000the repositioning of antiviral remedies and other medications. Several therapies, including\u0000oral antiviral treatments, represent some approaches to adapting to the long existence of the\u0000COVID-19 pandemic. In silico studies provide valuable insights throughout drug discovery and\u0000development in compliance with global efforts to overcome the pandemic. The main protease is\u0000an essential target in the viral cycle. Computer-aided drug design accelerates the identification\u0000of potential treatments, including oral therapy.\u0000\u0000\u0000\u0000This work aims to identify potential SARS-CoV-2 main protease inhibitors using different\u0000aspects of in silico approaches.\u0000\u0000\u0000\u0000In this work, we conducted a hierarchical virtual screening of SARS-CoV-2 main protease\u0000inhibitors. A similarity search was conducted to screen molecules similar to the inhibitor\u0000PF-07321332. Concurrently, structure-based pharmacophores, besides ligand-based pharmacophores,\u0000were derived. A drug-likeness filter filtered the compounds retrieved from similarity\u0000search and pharmacophore modeling before being subjected to molecular docking. The candidate\u0000molecules that showed higher affinity to the main protease than the reference inhibitor were\u0000further filtered by absorption, distribution, metabolism, and excretion (ADME) parameters.\u0000\u0000\u0000\u0000According to binding affinity and ADME analysis, four molecules (CHEMBL218022,\u0000PubChem163362029, PubChem166149100, and PubChem 162396459) were prioritized as\u0000promising hits. The compounds above were not reported before; no previous experimental studies\u0000and bioactive assays are available.\u0000\u0000\u0000\u0000Our time-saving approach represents a strategy for discovering novel SARS-CoV-\u00002 main protease inhibitors. The ultimate hits may be nominated as leads in discovering novel\u0000SARS-CoV-2 main protease inhibitors.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"671 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140479380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Policy Analysis on the Containment of Antimicrobial Resistance (AMR) in India: A Mixed Methods Study of Antimicrobial Stewardship as a Pivotal Intervention in Tackling AMR","authors":"Chetan Singh, Julia Lohmann, Anita Pandey, Lubhan Singh","doi":"10.2174/0122113525273938231221110816","DOIUrl":"https://doi.org/10.2174/0122113525273938231221110816","url":null,"abstract":"\u0000\u0000This policy report aimed at two goals, that is, to report the findings of the literature review and explore the perceptions of the key stakeholders in seeking better insight into the antimicrobial stewardship program (AMSP), and to develop antimicrobial resistance (AMR) policy recommendations for the Ministry of Health and Family Welfare (MoHFW), India, based on the findings from the rapid systematic review of the literature (both published and grey) and the views of key stakeholders.\u0000\u0000\u0000\u0000A mixed method approach using literature review and qualitative interviews has been applied. A rapid systematic literature review focusing on the antimicrobial stewardship pro-gram’s key achievements and its implementation and impact, implementation challenges, gaps and barriers, and opportunities, has been carried out, which has been followed by conducting interviews of key stakeholders and reporting the findings along with the recommendations.\u0000\u0000\u0000\u0000The findings have shown significant progress towards AMSP, such as expanding to 90 secondary-level hospitals and district-level hospitals/nursing homes, and the Indian Council of Medical Research antimicrobial resistance surveillance and research network (ICMR AMRSN) program. Education, training, and microbiological testing have been found to be the current focus areas. However, there exist challenges, including a lack of leadership support, diagnostic stew-ardship, and staffing of clinical pharmacists and infectious control nurses. Key gaps and barriers identified include setting up microbiology laboratories and hiring ICN nurses and clinical phar-macists. Opportunities have also been identified. Based on these findings, we have made succinct recommendations to address the themes and issues identified.\u0000\u0000\u0000\u0000Without new medicines, India will struggle to manage antimicrobial resistance. This situation calls for national oversight. This study has demonstrated AMSP as crucial for fighting this silent pandemic. The Indian government and policymakers must swiftly address critical chal-lenges, gaps, and opportunities. These findings and recommendations might potentially strengthen the future antimicrobial resistance national action plan (AMR NAP).\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"193 3-4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140490148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial and Antifungal Effects of Essential Oils from Origanum vulgare, Lavandula officinalis, and Syzygium aromaticum on Bacterial Strains\u0000through Gaseous Contact","authors":"Nabila Ainseba, Nabila Loukili, Amina Soulimane, Samia Bellifa, M. A. Dib, A. Muselli","doi":"10.2174/0122113525283890240108162525","DOIUrl":"https://doi.org/10.2174/0122113525283890240108162525","url":null,"abstract":"\u0000\u0000Hospital-acquired infections, also known as nosocomial infections, affect\u0000thousands of patients worldwide. In Algeria, these infections raise significant concerns and give\u0000rise to numerous questions due to hygiene deficits and non-compliance with preventive measures.\u0000\u0000\u0000\u0000The main objective of this study was to investigate the antibacterial and antifungal\u0000properties of Origanum vulgare, Lavandula officinalis, and Syzygium aromaticum, as well as their\u0000combinations, to discover new antibacterial and antifungal agents to combat nosocomial infections\u0000related to hospital and medical care environments.\u0000\u0000\u0000\u0000Essential oils were obtained by a Clevenger-type apparatus and analyzed\u0000using GC and GC/MS. The antimicrobial and antifungal activity was tested against several bacteria\u0000responsible for nosocomial infections in in-vitro tests using the gas contact method in sealed containers.\u0000\u0000\u0000\u0000The essential oil extracted from S. aromaticum buds was primarily composed of eugenol\u0000(59.4%), E-β-caryophyllene (16.5%), and eugenyl acetate (10.5%). The analysis of the chemical\u0000composition of L. officinalis essential oil identified 1,8-cineole (22.8%), β-pinene (12.4%), and\u0000linalool (8.5%) as the main compounds. As for O. vulgare essential oil, its major components were\u0000carvacrol (72.6%) and thymol (10.5%). The results revealed that the essential oils of L. officinalis,\u0000O. vulgare and S. aromaticum, as well as their combinations, used at a concentration of 1/10, had\u0000a remarkable effect on the E. coli, P. aeruginosa and K. pneumoniae strains. In contrast, they had\u0000a limited effect on the Gram-positive strain, S. aureus. The antifungal effectiveness of the essential\u0000oil of O. vulgare, as well as the combination of O. vulgare and S. aromaticum, has been remarkable\u0000against the C. albicans species, leading to a complete inhibition of yeast growth\u0000\u0000\u0000\u0000Our results indicate that our essential oils have a broad spectrum of antimicrobial\u0000activity, which makes them particularly useful as disinfectants in health facilities and could be\u0000used as a valuable medicine to control nosocomial infections and avoid infections acquired during\u0000a stay in a health facility such as respiratory tract infections and urinary tract infections.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"46 52","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140487341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cavity Disinfection with Natural Agents and their Efficacy: A Review on Recent Literature","authors":"Sreejeeta Dey, S. Deshmukh","doi":"10.2174/0122113525285948231215115207","DOIUrl":"https://doi.org/10.2174/0122113525285948231215115207","url":null,"abstract":"\u0000\u0000The success of a dental restoration can be altered by the amount of residual bacteria present under the cavity which over time cause deterioration of adhesive cement by microleakage or secondary caries. Cavity disinfectant application on the cavity walls performs a cleansing ac-tion to decrease the bacterial load and improve the longevity of restorations. Although a wide variety of such chemical disinfectants have been in use, their cytotoxic effects have led to the increasing popularity of natural agents. These materials possess antimicrobial, antioxidant and anti-inflammatory properties, which effectively disinfect cavity walls while, at the same time, being cheaper, less toxic, and more patient-friendly.\u0000Some of these agents have also been proven to improve the bond strength of resin to dentin by preventing collagen degradation and MMP inhibition. Propolis, aloe vera, chitosan, green tea, liquorice etc., are derived from parts of plants or animals and have been tested to be efficacious and, in some cases, superior to chemical alternatives without any erosive effect on dentin.\u0000Although there is a lack of enough in-vivo evidence to advocate the use of these products as an adjunct in dental therapy, recent studies have yielded promising results, which increases the scope for future clinical research. This review aims to highlight the properties and effectiveness of a few of such natural agents as potential cavity disinfectants.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"51 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139597869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Antibiogram of Escherichia coli Isolated from Children Under Five Years of Age Presented with Acute Diarrhoea: Cross Sectional Study from a Tertiary Care Centre in South India","authors":"Santhosh J. Thattil, Thekkuttuparambil A. Ajith","doi":"10.2174/0122113525274118231203153143","DOIUrl":"https://doi.org/10.2174/0122113525274118231203153143","url":null,"abstract":"\u0000\u0000The study aimed to analyze the prevalence and antibiogram of E. coli isolated from stool sample cultures collected from children below five years of age who were presented with acute diarrhoea in a tertiary care centre.\u0000\u0000\u0000\u0000Multidrug-resistant strains of diarrheagenic E. coliremain a major public health concern for greater morbidity and mortality. Antibiotic resistance and susceptibility patterns of E. coli were found to vary with geographical location.\u0000\u0000\u0000\u0000To determine the prevalence and antibiogram of E. coli isolated from cultures of diarrhoea stool samples collected from children below five years of age from laboratory records.\u0000\u0000\u0000\u0000A cross-sectional study was designed to analyze the report on stool culture of children (aged below five years) presented with acute diarrhea during the period between 2017 and 2020. The prevalence of E. coli and its antibiogram were analyzed. The data were subjected to statis-tical analysis.\u0000\u0000\u0000\u0000A total of 245 diarrhoea stool samples results were analyzed. E. coli was confirmed in 176 samples (72%). More number of isolates (51/176, 28.9%) were found in children below one year of age with male dominance. Amoxicillin resistance was found in all the E. coli strains isolated with no significant difference (p=0.2233) between genders and age groups below and above one year. A significant difference (p=0.0001) was found between male and female chil-dren of age below and above one year for cefotaxime and ciprofloxacin resistance. Polymyxin B (72%) followed by imipenem (69%) sensitivity was exhibited by the isolated E. coli strains.\u0000\u0000\u0000\u0000E. coli isolates were more sensitive to polymyxin B and imipenem while they were most resistant to amoxicillin. Effective antibiotic treatment strategies should be developed to control E. coli infections in children.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139598539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of TPC and TFC as Free Radical Scavengers and Microbial Growth Inhibitors in Himalayan Endemic Artemisia sieversiana Ehrhl Ex Willd. (Asteraceae) Plant from Northeastern, Pakistan","authors":"A. Hussain, Hassam Rasheed, Muhammad A. Khan, Syed A.I. Bokhari","doi":"10.2174/0122113525281671231220035432","DOIUrl":"https://doi.org/10.2174/0122113525281671231220035432","url":null,"abstract":"\u0000\u0000In various microorganisms, various defense mechanisms have evolved against the commercially available antimicrobial agents with increased resistance. Natural antimi-crobial agents of plant origin are better alternatives when an infectious disease arises due to resistant microbial strains. Here, we have evaluated the efficacy of total phenolics and total flavonoids with antioxidant and antimicrobial potential of Artemisia sieversiana Ehrhl Ex Willd. plant extracted with methanol, ethyl acetate, ethanol, n-hexane, and chloroform using soxhlet procedures\u0000\u0000\u0000\u0000The evaluation of TPC was achieved with Folin-Ciocalteu’s reagent method and quanti-tative estimation of TFC was done with the aluminum chloride colorimetric method. The antioxi-dant activities were estimated using FRSA-DPPH and TAC methods. The inhibitory activities of five solvent extracts of A. sieversiana against 2 gram-positive and 2 gram-negative pathogenic bac-terial strains (B. subtilis, P. aerogenosa, S. aureus, and E. coli) were evaluated using the well dif-fusion technique.\u0000\u0000\u0000\u0000The highest percentage yields of A. sieversiana extracts were obtained in ethanol (4.8 g, 12.1%) and methanol (4.01 g, 10%), while minimum extract yield was obtained in n-hexane (0.53 g, 1.34%). Both phenolics and flavonoids were higher in ethanol, methanol, and ethyl acetate ex-tracts while minimal in n-hexane extracts. Ethanol extract has shown maximum (69%) DPPH ac-tivity with a lower IC50 value (181 μg/ml), while the highest IC50 values of 330 and 325μg/ml were recorded for n-hexane and ethyl acetate extracts. The ethyl acetate and chloroform extracts dis-played overall highest TAC values. All the tested extracts of A. sieversiana exhibited variable in-hibitory effects in a dose-dependent manner against the tested bacterial strains with minimum 9.08 ± 0.23 to maximum 21.23 ± 7.04 mm inhibition zones. Methanol and ethyl acetate extracts at 2 to 4 mg/ml showed greater MIC results against P. aeruginosa in comparison to the B. subtilis strain.\u0000\u0000\u0000\u0000The extracts of A. sieversiana have been found to be rich in TPC and TFC with re-markable antibacterial and antioxidant efficacies, and the plant extracts could be employed as pos-sible alternatives to synthetic drugs in various nutraceutical and pharmaceutical industries.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"32 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139598215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Toll-like Receptor-3 Antagonist on Viral Asthma Exacerbations Via a TLR3/dsRNA Complex Pathway","authors":"Swamita Arora, Mohit Agrawal, K. Sahu, Sanjar Alam, Wasim Akram, Mohammad Khalid, Shivendra Kumar, S. Saha, Kuldeep Singh, Hema Chaudhary","doi":"10.2174/0122113525282849231228125935","DOIUrl":"https://doi.org/10.2174/0122113525282849231228125935","url":null,"abstract":"\u0000\u0000The Toll-like receptor-3 (TLR3) ligand Poly(I:C) has been shown to induce a viral aggravation of severe asthma by identifying double-stranded RNA (dsRNA). This study aimed to evaluate the therapeutic role of the TLR3/dsRNA complex inhibitor-calbiochem compound in the treatment of Poly(I:C)-induced viral asthma exacerbations through the ovalbu-min-induced asthma model in Swiss albino mice.\u0000\u0000\u0000\u0000Poly(I:C) and Ovalbumin drugs were injected in mice to sensitize (i.p. on 0, 7, and 14th day) and challenge (i.n. on the 21st and 22nd days). In contrast, the treatment drug TLR3/dsRNA complex inhibitor-calbiochem was given on the 21st and 22nd days intraperitoneally within the study period. In-vivo measurements were carried out in BALF and serum for pro-inflammatory cytokines, inflammatory leukocyte counts, lactate dehydrogenase (LDH) and nitrite levels, lungs/body weight index, and lung tissue histopathology using H and E staining in mice airways.\u0000\u0000\u0000\u0000High levels of cytokines (NF-κB, IL-1β, IL-5, RANTES, MIP-2, and MCP-1) are seen in groups exposed to OVA and Poly (I:C). Further, inflammatory leukocyte cell counts, lung-body weight (LW/BW) index, airway hyperresponsiveness (AHR), and lung tissue damage sug-gest exacerbations in mice airways. On the other hand, TLR3/dsRNA complex inhibitor-calbio-chem and dexamethasone significantly reversed these changes toward normal levels.\u0000\u0000\u0000\u0000These results suggest that the novel compound TLR3/dsRNA complex inhibitor-calbiochem has a better therapeutic role than dexamethasone for managing inflammatory char-acteristics in asthmatic mice lungs and is a potent target for viral asthma exacerbations\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"398 1-3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140502528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Phytoconstituents from Spathodea campanulata Flowers as Potential Antimalarial Agents","authors":"Abin V. Geevarghese, Maida Engels S.E., Ida Christi V. E., Poovarasan K. P., Sarulatha Sarulatha M. S., Thirumal P.","doi":"10.2174/0122113525275435231205111538","DOIUrl":"https://doi.org/10.2174/0122113525275435231205111538","url":null,"abstract":"\u0000\u0000Considering the majority of pharmaceutical firms focus on using herbal\u0000remedies as an alternative source of essential components, herbal remedies are extremely significant\u0000to pharmacological researchers. Spathodea campanulata is one of the members of the Bignoniaceae\u0000family. It is popular for its curative properties\u0000\u0000\u0000\u0000This research aimed to assess the possibility of bioactive elements and antioxidant impacts of\u0000the methanol fraction of Spathodea campanulata flowers.\u0000\u0000\u0000\u0000The objective of this research was to assess the achievable bioactive elements and antioxidant impacts of the methanol fraction of Spathodea campanulata flowers.\u0000\u0000\u0000\u0000GC-MS was adopted to identify the phytoconstituents present in the extract. In the present\u0000study, we utilized computational modelling with the Schrödinger Maestro 11.2 edition to make benefit of interactions among 42 bio-active components and anti-malarial targets (1LDG and 2ANL).\u0000\u0000\u0000\u0000In the methanol extract of the Spathodea campanulata flowers, phytochemical research revealed the presence of terpenoids, glycosides, carbohydrates, steroids, and flavonoids. Forty-two\u0000phytoconstituents, notably methyl-beta-d-galactopyranoside, 4-hydroxybenzoic acid, and 1,2-\u0000ethanediol monobenzoate, were determined through GC-MS analysis. Docking analysis of 42 bioactive compounds demonstrated that 1,2-ethanediol mono benzoate, 4-hydroxy benzoic acid, and methyl.beta.-d-galactopyranoside had higher G-Scores with 1LDG and 2ANL.\u0000\u0000\u0000\u0000In this work, multiple phytoconstituents discovered in a methanol extract of the S. campanulata flower were determined. As a result of this research, four phytoconstituents from the flower\u0000extracts may be created as an exciting new therapy for malaria.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"10 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140503001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANTIMICROBIAL STEWARDSHIP: SMART APPROACH TO COMBAT ANTIBIOTIC RESISTANCE","authors":"Manoj S. Dikkatwar, Sharad Chand, Treesa P. Varghese, Shrishti Shandily, Jeetu Biswas, Supriya Roy, Jitendra Vagashiya, Rakesh Kumar Singh","doi":"10.2174/0122113525274628231220062819","DOIUrl":"https://doi.org/10.2174/0122113525274628231220062819","url":null,"abstract":"\u0000\u0000Antimicrobial resistance (AMR) is a major public health concern worldwide. It raises morbidity and mortality and is connected with substantial/significant economic costs. Effective prevention and treatment of an increasing number of diseases caused by pathogens that can no longer be treated with conventional drugs are threatened by antimicrobial re-sistance. AMS programme helps to encourage the appropriate use of antimicrobials. The rise and spread of antibiotic resistance and strategies to combat it are the main topics of this review. Antimicrobial stewardship programme is a healthcare strategy that optimizes the use of anti-biotics and promotes the appropriate use of antimicrobials through the adoption of evidence-based interventions. AMS programme helps to encourage the right use of antimicrobials. This coordinated approach enhances patient outcomes, reduces microbial resistance, and slows the spread of diseases brought on by multidrug-resistant organisms. The growth of antibiotic re-sistance and the strategies for battling it have been the main topics of this review.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"120 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139616243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Pharmacophore Modeling, 3D-atom-based QSAR, ADMET, Dock-ing, and Molecular Dynamics Studies for the Development of Psoralen-based Derivatives as Antifungal Agents","authors":"Kalyani D. Asgaonkar, Shital M. Patil, Trupti S Chitre, Arati Prabhu, Krishna S. Shevate, Ashwini K. Sagar, Akshata P. Naik","doi":"10.2174/0122113525279683231228130206","DOIUrl":"https://doi.org/10.2174/0122113525279683231228130206","url":null,"abstract":"\u0000\u0000The mortality and morbidity rates in patients caused by fungi are ex-tremely high. 3-4 % of species of fungi like Candida and Aspergillus are responsible for >99% of invasive fungal infections.\u0000\u0000\u0000\u0000The goal of the current work was to use several In-silico methods, such as Pharmacophore modeling and 3D-QSAR, to design New chemical entities (NCEs) that have antifungal activity.\u0000\u0000\u0000\u0000A dataset of 40 Psoralen derivatives was taken from available literature, and then, the pharmacophore hypothesis and 3D-QSAR model development were generated using Schrodinger 2023-1 software. After designing a library of 36 compounds, they were sub-jected to ADMET prediction. Screened compounds from the ADMET study were docked with 14 alpha demethylase CYP51 (PDB ID: 3LD6) using Schrödinger software. Molecular dynam-ics (MD) simulation studies were performed on PDB-3LD6 using Desmond-v7.2.\u0000\u0000\u0000\u0000The top-ranked hypothesis, AHRRR_1, was taken into consideration when designing the library of potential NCEs.In order to check the drug likeliness of the com-pounds, all 36 designed NCEs were subjected to ADMET prediction using the QikProp tool. The majority of compounds have a good partition coefficient index (less than five). Qplog HERG value was found to be less, making them safer and less toxic. C- 4, 6, 9, 13, 15, 22, 24, 27, 31, and 33 have shown compliance with Lipinski’s rule with zero violations. Compounds C-9, C-13, C-22, C-24, and C-27 have shown better docking scores than the standard Ketocon-azole. Compounds C-9, 24, and 27 have shown a greater number of hydrophobic and hydrogen bond interactions in comparison with the other compounds. Compounds 9, 24, and 27 showed good stability after 100ns molecular simulation simulations.\u0000\u0000\u0000\u0000\u0000In the current work, the application of insilico methods such as pharmacophore hypothesis, 3D QSAR, ADMET study, docking, and simulation studies have helped to optimize Psoralen pharmacophore for potential antifungal activity. Therefore, the outcomes of the present study could provide insights into the discovery of new potential alpha demethylase inhibitors with improved selectivity and activity against fungal infections.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140505149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}