scholarly journals IN SILICO STUDY OF CEPHALOSPORIN DERIVATIVES TO INHIBIT THE ACTIONS OF Pseudomonas aeruginosa

2021 ◽  
Vol 7 (2) ◽  
pp. 296-303
Author(s):  
Saly Amaliacahya Aprilian ◽  
Firdayani Firdayani ◽  
Susi Kusumaningrum
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Protein Data Bank ◽  
In Silico ◽  
Binding Proteins ◽  
Antimicrobial Agents ◽  
Data Bank ◽  
Multi Drug Resistance ◽  
3D Interaction ◽  
Penicillin Binding Proteins

Studi In Silico Senyawa Turunan Sefalosporin dalam Menghambat Aktivitas Bakteri Pseudomonas aeruginosa Infeksi yang diakibatkan oleh bakteri gram-negatif, seperti Pseudomonas aeruginosa telah menyebar luas di seluruh dunia. Hal ini menjadi ancaman terhadap kesehatan masyarakat karena merupakan bakteri yang multi-drug resistance dan sulit diobati. Oleh karena itu, pentingnya pengembangan agen antimikroba untuk mengobati infeksi semakin meningkat dan salah satu yang saat ini banyak dikembangkan adalah senyawa turunan sefalosporin. Penelitian ini melakukan studi mengenai interaksi tiga dimensi (3D) antara antibiotik dari senyawa turunan Sefalosporin dengan penicillin-binding proteins (PBPs) pada P. aeruginosa. Tujuan dari penelitian ini adalah untuk mengklarifikasi bahwa agen antimikroba yang berasal dari senyawa turunan sefalosporin efektif untuk menghambat aktivitas bakteri P. aeruginosa. Struktur PBPs didapatkan dari Protein Data Bank (PDB ID: 5DF9). Sketsa struktur turunan sefalosporin digambar menggunakan Marvins Sketch. Kemudian, studi mengenai interaksi antara antibiotik dan PBPs dilakukan menggunakan program Mollegro Virtual Docker 6.0. Hasil yang didapatkan yaitu nilai rerank score terendah dari kelima generasi sefalosporin, di antaranya sefalotin (-116.306), sefotetan (-133.605), sefoperazon (-160.805), sefpirom (-144.045), dan seftarolin fosamil (-146.398). Infections caused by gram-negative bacteria, such as Pseudomonas aeruginosa, have been spreading worldwide. It is a threat to public health because of its multi-drug resistance and difficulty to treat. Therefore, the demand for developing antimicrobial agents to treat infections is increasing. One of them that is currently under development is cephalosporin derivative compounds. This research studied the three-dimensional (3D) interaction between antibiotics from cephalosporin derivatives and penicillin-binding proteins (PBPs) in P. aeruginosa. This study aimed to clarify whether the cephalosporin derivatives were effective in inhibiting the activity of P. aeruginosa. The PBPs structure was obtained from the Protein Data Bank (PDB ID: 5DF9). The structural sketch of the cephalosporin derivative was drawn using the Marvins Sketch, whereas the study on the interaction between antibiotics and PBPs was carried out using the Mollegro Virtual Docker 6.0 program. The results showed the lowest rerank score from five cephalosporin derivatives, namely cephalotin (-116,306), cephotetan (-133.605), cephoperazone (-160.805), cephpirome (-144.045), and cephtaroline fosamil (-146.398).

scholarly journals Antibiotic profiling of Pseudomonas aeruginosa isolates from pus sample of rural tertiary care hospital of Western Maharashtra, Loni, India

2017 ◽  
Vol 5 (7) ◽  
pp. 3076 ◽  
Author(s):  
Namita A., Raytekar, ◽  
Meghna R. Choudhari ◽  
Sonali Das
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Antimicrobial Agents ◽  
Tertiary Care ◽  
Opportunistic Pathogen ◽  
Multi Drug Resistance ◽  
Resistance Pattern ◽  
Care Hospital ◽  
Medical College

Background: Pseudomonas aeruginosa (P. aeruginosa) considered as an opportunistic pathogen which can be isolated from various kinds of infection. The risk of emergence of antibiotic resistance is based on different antibiotic treatments. Antibiotic resistance and flexibility to adapt changing environment renders the pathogens a matter of concern in hospital acquired infections. Changing pattern of antimicrobial resistance pose challenge in treating pyogenic infections, hence periodical monitoring of bacterial profile and their antibiotic susceptibility pattern is important. This study deals with the infectious and drug resistance nature of P. aeruginosa with effectiveness of antimicrobial agents against it.Methods: Present study was conducted in Centre for Biotechnology, Pravara Institute of Medical Sciences, Loni, Maharashtra, India. A total of 763 pus samples were received in the bacteriology section of department of microbiology, rural medical college, Loni from the various wards of Pravara Rural Hospital. The colonial morphology and identification was done as per standard microbiology procedures. Antibiogram testing was done as per Kirby Bauer disc diffusion method.Results: Out of 763 pus samples 154 were Pseudomonas aeruginosa thus showing 20.19% prevalence. In this study, it was observed that isolates were sensitive to Ciprofloxacin (76.63%) followed by Amikacin. However, showed 90.90 % resistant to Cefazolin followed by Co-trimoxazole 75.97% was observed. Multi drug resistance (MDR) strain 68.83% (N=106) was detected from 154 isolates strains of Pseudomonas aeruginosa. Prevalent resistance pattern was found to be GENr, AKr, CAZr, CZr, COTr for 10 (9.43%) isolates followed by GENr, CAZr, CZr, MRPr, COTr, CIPr for 9 (8.49%) isolates.Conclusions: Present study focused on antibiotic resistance pattern of P. aeruginosa from pus sample. This study contributes in understanding the emergence of MDR strains which can be considered for judicial usage of antibiotics in hospital settings. 

scholarly journals La acelerada búsqueda de candidatos terapéuticos contra SARS-CoV-2, métodos in silico: Revisión

2020 ◽  
Vol 7 (3) ◽  
pp. 347-362
Author(s):  
Oscar Cobar ◽  
Rodrigo J. Vargas
Keyword(s):  
Protein Data Bank ◽  
In Silico ◽  
Data Bank

El reposicionamiento de fármacos como la derivatización química, que se han aplicado en los estudios de descubrimiento y diseño de fármacos contra el SARS-CoV-2, dependen del ciclo de vida del virus, las dianas moleculares identificadas y un diseño basado en su estructura e interacciones moleculares. Se realizó una revisión extensa en las bases de datos públicas e institucionales RSCB-Protein Data Bank, ZINC, NCBI (PubMed, PMC), PubChem, Science Direct e instituciones como CDC, NIH y revistas científicas especializadas sobre los avances en la búsqueda de nuevas moléculas contra el nuevo coronavirus basadas en estudios in silico, detectándose más de 40,000 publicaciones sobre SARS-CoV-2 y cerca de 200 relacionadas a dichos estudios, las consideradas más relevantes fueron analizadas e incluidas en este artículo. Su análisis evidencia el avance acelerado de las herramientas computacionales y fortaleza del diseño de fármacos asistido por computadora (in silico approach) para la generación de nuevas moléculas con posibilidad de ser activas contra COVID-19 y presenta las principales dianas moleculares sobre la que actúan estos agentes con potencial antiviral.

scholarly journals BUSCA DE MOLÉCULAS COM ATIVIDADE BRONCODILATADORA NA ESPÉCIE MIKANIA GLOMERATA SPRENG EMPREGANDO FERRAMENTAS IN SILICO

2020 ◽  
Vol 6 (15) ◽  
Author(s):  
Letícia Fernandes Fraga ◽  
Leonardo Luiz Borges
Keyword(s):  
Protein Data Bank ◽  
In Silico ◽  
Data Bank ◽  
Mikania Glomerata

Este estudo tem por objetivo avaliar os principais compostos que expliquem a atividade broncodilatadora da Mikania glomerata Spreng, empregando ferramentas in silico. Os metabólitos do guaco foram levantados bibliograficamente e a codificação das moléculas para a realização das predições foi obtida no site Pubchem. Realizou-se então triagem de bioatividade com os programas SwissADME, ProToxII, PASS e Molinspiration e pesquisa de alvos, com os servidores SuperPred Webserver. Após a identificação do alvo, a estrutura selecionada foi obtida pelo site Protein Data Bank (PDB) para o docking molecular com o programa GOLD. Os metabólitos da Mikania glomerata Spreng tiveram suas propriedades físico-químicas e biológicas analisadas. Os alvos para o docking molecular foram identificados e verificados para cada composto, com suas respectivas estruturas cristalografadas no Protein Data Bank (PDB). A molécula de cumarina foi selecionada pois apresentou predição de interação com o receptor muscarínico M3 (ID: 4DAJ). O docking revelou interação da cumarina com o receptor M3, o que poderia auxiliar na explicação para os efeitos broncodilatadores desta espécie vegetal. O estudo in silico do guaco, abordado neste trabalho, elegeu a cumarina como principal metabólito ativo com possível atividade broncodilatadora presente na Mikania glomerata Spreng. O docking da cumarina mostrou ancoragem desta molécula no sítio ativo do receptor muscarínico M3 devido as atividades desta espécie, assim, este marcador poderia atuar como antagonista desse receptor, apresentando possível atividade parassimpatolítica e, portanto, broncodilatadora.

scholarly journals ANALYSIS OF MOLECULAR DOCKING EFFICIENCY OF CLEISTANTHIN-A, AS AN ALTERNATIVE FOR NICOTINE ADDICTION

2018 ◽  
Vol 10 (4) ◽  
pp. 98
Author(s):  
A. Amala Lourthuraj ◽  
M. Masilamani Selvam ◽  
Bharathi Ravikrishnan ◽  
M. Vinoth ◽  
Waheeta Hopper
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Protein Data Bank ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
High Throughput ◽  
In Silico ◽  
Data Bank ◽  
Tobacco Consumption ◽  
Nicotinic Acetylcholine

Objective: The present research was aimed to understand the molecular docking efficiency of a plant-derived compound cleistanthin-A and a common ingredient in tobacco consumption nicotine with nicotinic acetylcholine receptor (nAChR).Methods: The 3-D structure of nAChR was retrieved from the protein data bank (ID 5AFH). Ligand was obtained from the PUBCHEM. The in silico protocol comprised of three steps: high-throughput virtual screening (HTVS), standard preci­sion (SP) and extra precision (XP). The screened molecules were ranked accordingly using glide score. Schrödinger tool was used to perform the docking analysis.Results: The binding efficiency of the nicotine and cleistanthin-A was found to be docked at the cys-cys loop of the receptor. Based upon the glide score and glide energy it can be reported that, nicotine binding can be inhibited by the binding of cleistanthin-A to the nAChR.Conclusion: The docking efficiency of cleistanthin-A was good compared to nicotine towards nAChR. Hence, cleistanthin–A was derived as a better choice as an alternative for nicotine in smoke therapy.

scholarly journals An usual approach to treatment of a case of multidrug resistance Pseudomonas aeruginosa peritonitis: parenteral and intraperitoneal aminoglycosides and parenteral colistin

2012 ◽  
Vol 4 (1) ◽  
pp. 36 ◽  
Author(s):  
Ian May ◽  
Maha Abu-Khdeir ◽  
Roland Alexander Blackwood
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Drug Resistance ◽  
Intensive Care ◽  
Multidrug Resistance ◽  
Pleural Cavity ◽  
Abdominal Cavity ◽  
Multi Drug Resistance ◽  
Clinical Settings ◽  
Intravenous Antibiotics ◽  
Polymyxin E

Infections caused by <em>Pseudomonas aeruginosa </em>are becoming more common and increasingly more difficult to treat due to the continued development of drug resistance. While sensitivity to colistin (polymyxin E) is well known, it is frequently avoided due to concerns of nephrotoxicity. Reported here is a case of a multi-drug resistance pseudomonal typhlitis, bacteremia and pleural cavity infection that required significant intensive care, and serial abdominal washouts. Intra-peritoneal tobramycin in combination with broad-spectrum intravenous antibiotics including colistin were used. Several instillations of tobramycin into the abdominal cavity along with concomitant IV administration of colistin, ceftazidime and tobramycin and<em> per os</em> colistin, tobramycin and nystatin resulted in the clearance of the pseudomonal infection without any evidence of toxicity from the treatment. Intra-abdominal tobramycin with parenteral colistin therapy can be used in complicated clinical settings with appropriate nephroprotection.

scholarly journals Affinity of Tomopenem (CS-023) for Penicillin-Binding Proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa

2008 ◽  
Vol 53 (3) ◽  
pp. 1238-1241 ◽  
Author(s):  
Tetsufumi Koga ◽  
Chika Sugihara ◽  
Masayo Kakuta ◽  
Nobuhisa Masuda ◽  
Eiko Namba ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Binding Proteins ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
High Affinity

ABSTRACT Tomopenem (formerly CS-023), a novel 1β-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.

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