Pub Date : 2021-01-01DOI: 10.1504/ijcbdd.2021.10043848
Maham Sarvat, Suhaib Masroor, Mohammad Muzammil Khan
{"title":"Telemetric drug injection system with centralised monitoring and control of multiple injectors","authors":"Maham Sarvat, Suhaib Masroor, Mohammad Muzammil Khan","doi":"10.1504/ijcbdd.2021.10043848","DOIUrl":"https://doi.org/10.1504/ijcbdd.2021.10043848","url":null,"abstract":"","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"39 1","pages":"364-376"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87488712","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}
Pub Date : 2020-06-29DOI: 10.1504/ijcbdd.2020.107892
Vidhya Gopalakrishnan, A. Nambiar, Sukanya Basu, G. Madhuvanthi
Diabetic retinopathy (DR) is the leading causes of blindness in many countries. Proteomic studies of DR have discovered a set of genes involved in the disease. In this study, protein protein interaction network (PPIN) of DR proteins were analysed to identify the hub nodes and a PPI network related to retinopathy genes was generated using Cytoscape software. The constructed protein network was analysed using ClusterONE, ClueGO and cytohubba. Among 497 identified candidate proteins, 482 were seen in the main connected component. The topology and functionality of the associated proteins were studied based on centrality parameters such as degree, betweenness and closeness. From the result, two significant clusters were identified which included the experimentally proven five seed proteins. These findings helped in identifying important hub proteins and their direct interacting partners that could be considered as therapeutic biomarkers for treating disease.
糖尿病视网膜病变(DR)是许多国家致盲的主要原因。对糖尿病的蛋白质组学研究发现了一组与该病有关的基因。本研究通过分析DR蛋白的蛋白相互作用网络(protein protein interaction network, PPIN)来识别中枢节点，并利用Cytoscape软件生成与视网膜病变基因相关的蛋白相互作用网络。用ClusterONE、ClueGO和cytohubba分析构建的蛋白网络。在鉴定的497个候选蛋白中，有482个位于主要连接成分中。基于中心性参数，如度、中间度和接近度，研究了相关蛋白的拓扑结构和功能。从结果中，确定了两个重要的簇，其中包括实验证明的五种种子蛋白。这些发现有助于确定重要的枢纽蛋白及其直接相互作用的伙伴，这些伙伴可以被认为是治疗疾病的治疗性生物标志物。
{"title":"PPI network analysis of diabetic retinopathy genes","authors":"Vidhya Gopalakrishnan, A. Nambiar, Sukanya Basu, G. Madhuvanthi","doi":"10.1504/ijcbdd.2020.107892","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.107892","url":null,"abstract":"Diabetic retinopathy (DR) is the leading causes of blindness in many countries. Proteomic studies of DR have discovered a set of genes involved in the disease. In this study, protein protein interaction network (PPIN) of DR proteins were analysed to identify the hub nodes and a PPI network related to retinopathy genes was generated using Cytoscape software. The constructed protein network was analysed using ClusterONE, ClueGO and cytohubba. Among 497 identified candidate proteins, 482 were seen in the main connected component. The topology and functionality of the associated proteins were studied based on centrality parameters such as degree, betweenness and closeness. From the result, two significant clusters were identified which included the experimentally proven five seed proteins. These findings helped in identifying important hub proteins and their direct interacting partners that could be considered as therapeutic biomarkers for treating disease.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"25 1","pages":"302-315"},"PeriodicalIF":0.0,"publicationDate":"2020-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91233997","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}
Pub Date : 2020-06-29DOI: 10.1504/ijcbdd.2020.10030164
S. Ariya, B. Joseph, J. Christy
Cancer is one of the leading causes of death worldwide. Though advanced treatment options are available, a cure for this disease is still unidentified. This work is aimed at the identification of drugs to target the matrix metallopeptidase, a major protein overexpressed in this disease. Two hundred and forty seven active phytochemicals from the medicinal plant Ipomea sepiaria were taken as the lead drugs and molecular docking analysis as well as interaction studies were carried out. The binding affinity for each ligand with the target was determined along with Molecular dynamic simulation of the complex to determine the stability of the complex in the system. Thus eight drugs namely Tetradecanoic acid, Nerolidol, Ipomeanine, Dibutyl phthalate, Cis-Caffeic acid, Caffeic acid, Moupinamide and N-Cis-Feruloyltyramine were found to be the most promising drugs for treating cancer. They outperformed the scores of four different drugs available in the market.
{"title":"Exploring the antineoplastic effect of phytochemicals from Ipomea sepiaria against matrix metallopeptidases: a pharmacoinformatics approach","authors":"S. Ariya, B. Joseph, J. Christy","doi":"10.1504/ijcbdd.2020.10030164","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.10030164","url":null,"abstract":"Cancer is one of the leading causes of death worldwide. Though advanced treatment options are available, a cure for this disease is still unidentified. This work is aimed at the identification of drugs to target the matrix metallopeptidase, a major protein overexpressed in this disease. Two hundred and forty seven active phytochemicals from the medicinal plant Ipomea sepiaria were taken as the lead drugs and molecular docking analysis as well as interaction studies were carried out. The binding affinity for each ligand with the target was determined along with Molecular dynamic simulation of the complex to determine the stability of the complex in the system. Thus eight drugs namely Tetradecanoic acid, Nerolidol, Ipomeanine, Dibutyl phthalate, Cis-Caffeic acid, Caffeic acid, Moupinamide and N-Cis-Feruloyltyramine were found to be the most promising drugs for treating cancer. They outperformed the scores of four different drugs available in the market.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"20 1","pages":"255-271"},"PeriodicalIF":0.0,"publicationDate":"2020-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75876169","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}
Pub Date : 2020-06-23DOI: 10.1504/ijcbdd.2020.107888
S. Cosmas, Olanrewaju Ayodeji Durojaye, P. Joshua, J. Ogidigo, Collins Audu Difa, Justus Nmaduka Nwachukwu
Introduction: Malaria is one of the most common diseases that threaten many of the subtropical and tropical regions. Countries where the risk of transmission of malaria is at the high rate are over a hundred currently and these counties are being visited by over 125, 000, 000 international travelers on yearly basis. Materials and Methods: Chemical structures of ligands were drawn with the MarvinSketch software and converted into SMILES strings for the calculation of pharmacokinetic parameters. Results: The predicted binding energies between the three selected antifolate drugs, gedunin, its derivatives (C=O, C2H5, C3H6O2, C4H8O2, CONH2, NH2, OCH3, OH) and the Plasmodium falciparium DHFR enzyme were -8.0, -7.5, -8.0, -9.5, -9.0, -8.4, -8.9, -8.2, -8.9, -8.7, -8.3, -8.4 Kcal/mol respectively. Conclusion: The results from the experiment showed that gedunin and its modified derivatives might be better antimalarial agents than the antifolate drugs as revealed by the predicted binding energies between the target enzyme and the ligands.
{"title":"Comparative in-silico parmacokinetics and molecular docking study on gedunin isolated from Azadirachta indica, its modified derivatives and selected antifolate drugs as potential dihydrofolate reductase inhibitors of Plasmodium falciparum","authors":"S. Cosmas, Olanrewaju Ayodeji Durojaye, P. Joshua, J. Ogidigo, Collins Audu Difa, Justus Nmaduka Nwachukwu","doi":"10.1504/ijcbdd.2020.107888","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.107888","url":null,"abstract":"Introduction: Malaria is one of the most common diseases that threaten many of the subtropical and tropical regions. Countries where the risk of transmission of malaria is at the high rate are over a hundred currently and these counties are being visited by over 125, 000, 000 international travelers on yearly basis. Materials and Methods: Chemical structures of ligands were drawn with the MarvinSketch software and converted into SMILES strings for the calculation of pharmacokinetic parameters. Results: The predicted binding energies between the three selected antifolate drugs, gedunin, its derivatives (C=O, C2H5, C3H6O2, C4H8O2, CONH2, NH2, OCH3, OH) and the Plasmodium falciparium DHFR enzyme were -8.0, -7.5, -8.0, -9.5, -9.0, -8.4, -8.9, -8.2, -8.9, -8.7, -8.3, -8.4 Kcal/mol respectively. Conclusion: The results from the experiment showed that gedunin and its modified derivatives might be better antimalarial agents than the antifolate drugs as revealed by the predicted binding energies between the target enzyme and the ligands.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"10 1","pages":"237-254"},"PeriodicalIF":0.0,"publicationDate":"2020-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85012725","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}
Pub Date : 2020-06-23DOI: 10.1504/ijcbdd.2020.107891
Aditi Rathee, K. Gupta, S. Kumari, S. Chhibber, Ashok Kumar
Bacteria possess a protective extracytoplasmic glycopeptide polymer, i.e., peptidoglycan. In case of Gram-positive bacteria, it acts as scaffolds to many virulence factors whereas in Gram-negative bacteria, it serves as an anchor to outer membrane. Many antibiotics act on bacteria by inhibiting the activity of enzymes involved in the synthesis of peptidoglycan. However during the years, overexposure of antibiotics has led to modification of peptidoglycan chain by bacteria viz. N-deacetylation, N-glycolylation and O-acetylation, etc. Peptidoglycan hydrolases are known to play an important role in the suppression of bacterial infections as a component of the innate immune system as well as disintegrating peptidoglycan which is an important factor in the pathogenesis of various organisms. Present study explicates computational analysis of a peptidoglycan hydrolase enzyme from a total of 41 fully sequenced genomes of Serratia marcescens and other Serratia species. Seventy-five unique motifs were identified among the protein sequences of peptidoglycan hydrolase.
{"title":"In-silico analysis of peptidoglycan hydrolases from Serratia marcescens and other Serratia species","authors":"Aditi Rathee, K. Gupta, S. Kumari, S. Chhibber, Ashok Kumar","doi":"10.1504/ijcbdd.2020.107891","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.107891","url":null,"abstract":"Bacteria possess a protective extracytoplasmic glycopeptide polymer, i.e., peptidoglycan. In case of Gram-positive bacteria, it acts as scaffolds to many virulence factors whereas in Gram-negative bacteria, it serves as an anchor to outer membrane. Many antibiotics act on bacteria by inhibiting the activity of enzymes involved in the synthesis of peptidoglycan. However during the years, overexposure of antibiotics has led to modification of peptidoglycan chain by bacteria viz. N-deacetylation, N-glycolylation and O-acetylation, etc. Peptidoglycan hydrolases are known to play an important role in the suppression of bacterial infections as a component of the innate immune system as well as disintegrating peptidoglycan which is an important factor in the pathogenesis of various organisms. Present study explicates computational analysis of a peptidoglycan hydrolase enzyme from a total of 41 fully sequenced genomes of Serratia marcescens and other Serratia species. Seventy-five unique motifs were identified among the protein sequences of peptidoglycan hydrolase.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"1 1","pages":"282-301"},"PeriodicalIF":0.0,"publicationDate":"2020-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75710246","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}
Pub Date : 2020-06-23DOI: 10.1504/ijcbdd.2020.107893
B. Bharathi, P. B. Shamily
Iris is an evenly highlighted radial membrane with complex patterns that are perceptible upon near inspection, which exists behind the cornea of the eye with a changeable circular opening called the pupil. Iris Recognition System is a technique of identifying people using those complex distinctive features in patterns. Generally, Iris recognition system is used in security allied applications such as, authenticating PCs, network and mobile devices, physical and logical premises access control, national border control, secure banking and financial transactions, national identity like AADHAAR in India etc. This paper reviews the state-of-art design and implementation of various iris recognition systems. The contributions of the paper include: 1) conferring the importance, applications and deployment of iris recognition system related to human identification; 2) providing an analysis on iris recognition methods in effect; 3, discussing the present research defies; 4) providing commendations for the future research on iris recognition system.
{"title":"A review on iris recognition system for person identification","authors":"B. Bharathi, P. B. Shamily","doi":"10.1504/ijcbdd.2020.107893","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.107893","url":null,"abstract":"Iris is an evenly highlighted radial membrane with complex patterns that are perceptible upon near inspection, which exists behind the cornea of the eye with a changeable circular opening called the pupil. Iris Recognition System is a technique of identifying people using those complex distinctive features in patterns. Generally, Iris recognition system is used in security allied applications such as, authenticating PCs, network and mobile devices, physical and logical premises access control, national border control, secure banking and financial transactions, national identity like AADHAAR in India etc. This paper reviews the state-of-art design and implementation of various iris recognition systems. The contributions of the paper include: 1) conferring the importance, applications and deployment of iris recognition system related to human identification; 2) providing an analysis on iris recognition methods in effect; 3, discussing the present research defies; 4) providing commendations for the future research on iris recognition system.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"49 1","pages":"316-331"},"PeriodicalIF":0.0,"publicationDate":"2020-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82195722","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}
Pub Date : 2020-06-23DOI: 10.1504/ijcbdd.2020.10030171
S. Sunkar, M. Aravind, S. Reddy, D. Neeharika
WNT pathway is generally involved in controlling gene expression and cell behaviour. Earlier studies revealed that mutations in genes of WNT pathway lead to different types of cancer. In our study, cancer related novel gene candidate, WNT inhibitory factor 1 (WIF1) involved in WNT pathway was analysed for potentially deleterious non-synonymous single nucleotide polymorphisms (SNPs). From the dbSNP, the SNPs were retrieved and analysed using various computational tools for their pathogenicity and stability. A total of 36 mutations were identified to be deleterious and decrease the stability. The WIF domain region was considered where the mutations A73E, A73V, R71G were found to be potentially deleterious. These proteins with and without mutations were modelled and compared. Further, it was identified that three deleterious mutations were in the WIF1 protein binding site 1 suggesting their possible role in disease mechanism and can be considered as a potential drug target for various cancers in humans.
{"title":"In silico approach for the prediction of functional nsSNPs in WIF1 gene of WNT pathway","authors":"S. Sunkar, M. Aravind, S. Reddy, D. Neeharika","doi":"10.1504/ijcbdd.2020.10030171","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.10030171","url":null,"abstract":"WNT pathway is generally involved in controlling gene expression and cell behaviour. Earlier studies revealed that mutations in genes of WNT pathway lead to different types of cancer. In our study, cancer related novel gene candidate, WNT inhibitory factor 1 (WIF1) involved in WNT pathway was analysed for potentially deleterious non-synonymous single nucleotide polymorphisms (SNPs). From the dbSNP, the SNPs were retrieved and analysed using various computational tools for their pathogenicity and stability. A total of 36 mutations were identified to be deleterious and decrease the stability. The WIF domain region was considered where the mutations A73E, A73V, R71G were found to be potentially deleterious. These proteins with and without mutations were modelled and compared. Further, it was identified that three deleterious mutations were in the WIF1 protein binding site 1 suggesting their possible role in disease mechanism and can be considered as a potential drug target for various cancers in humans.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"21 1","pages":"332-345"},"PeriodicalIF":0.0,"publicationDate":"2020-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84674891","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}
Pub Date : 2020-06-23DOI: 10.1504/ijcbdd.2020.107890
P. Singh
Central lethality rule suggests that hub proteins are the most important and their deletion leads to more damage to biological networks as compared to non-hub proteins. Hub proteins present towards the core of protein-protein interaction (PPI) network are considered to be more important in comparison to proteins at the periphery. The k-shell decomposition method generates k-shell index which indicates the local and global importance of a protein in PPI network. But there is no method till now reported which can differentiate among the proteins with same k-shell index. In this work attempt has been made to add parameter Inter k-shell connectivity to differentiate proteins with same k-shell index and exploring their biological importance.
{"title":"Inter k-shell connectivity: a novel computational approach to identify drug targets","authors":"P. Singh","doi":"10.1504/ijcbdd.2020.107890","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.107890","url":null,"abstract":"Central lethality rule suggests that hub proteins are the most important and their deletion leads to more damage to biological networks as compared to non-hub proteins. Hub proteins present towards the core of protein-protein interaction (PPI) network are considered to be more important in comparison to proteins at the periphery. The k-shell decomposition method generates k-shell index which indicates the local and global importance of a protein in PPI network. But there is no method till now reported which can differentiate among the proteins with same k-shell index. In this work attempt has been made to add parameter Inter k-shell connectivity to differentiate proteins with same k-shell index and exploring their biological importance.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"73 1","pages":"272-281"},"PeriodicalIF":0.0,"publicationDate":"2020-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80456741","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}
Pub Date : 2020-05-10DOI: 10.1504/ijcbdd.2020.10029438
J. Ntaganda
This paper aims at designing a two compartmental mathematical model for determining the response of protein (Interferon) and drug (Ribarivin) for a patient who is suffering from hepatitis C virus (HCV). The stability of developed mathematical model is established. Using inverse techniques, model parameters and functions are identified. To test efficiency and response to interferon and ribavirin as HCV treatment, the validation of the mathematical model is achieved by considering a patient on treatment during 12 months. The results obtained are rather satisfactory since model parameters vary around their corresponding value that is equilibrium values for healthy subjects. Furthermore, the reaction of the disease to treatment can be modelled and a feedback can be approximated by the solution of an optimal control problem. The increasing necessity to interpret the meaning of measurable variables such as interferon and ribavirin under both physiological and pathological conditions for a patient has imposed the need for relatively simple models that should be able to describe as accurately as possible the mechanical behaviour of the disease.
{"title":"Mathematical modelling of hepatitis C virus dynamics response to therapeutic effects of interferon and ribavirin","authors":"J. Ntaganda","doi":"10.1504/ijcbdd.2020.10029438","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.10029438","url":null,"abstract":"This paper aims at designing a two compartmental mathematical model for determining the response of protein (Interferon) and drug (Ribarivin) for a patient who is suffering from hepatitis C virus (HCV). The stability of developed mathematical model is established. Using inverse techniques, model parameters and functions are identified. To test efficiency and response to interferon and ribavirin as HCV treatment, the validation of the mathematical model is achieved by considering a patient on treatment during 12 months. The results obtained are rather satisfactory since model parameters vary around their corresponding value that is equilibrium values for healthy subjects. Furthermore, the reaction of the disease to treatment can be modelled and a feedback can be approximated by the solution of an optimal control problem. The increasing necessity to interpret the meaning of measurable variables such as interferon and ribavirin under both physiological and pathological conditions for a patient has imposed the need for relatively simple models that should be able to describe as accurately as possible the mechanical behaviour of the disease.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"37 1","pages":"169-180"},"PeriodicalIF":0.0,"publicationDate":"2020-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79268169","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}
Pub Date : 2020-05-10DOI: 10.1504/ijcbdd.2020.10029437
R. Kalirajan, A. Pandiselvi, B. Gowramma
9-Aminoacridines are known DNA-intercalating agents, due to antiproliferative properties. Anticancer agents with 9-aminoacridines like amascrine, and nitracrine were developed. Docking studies were performed for isoxazole substituted 9-aminoacridines 1a-x as selective HER2 inhibitors (PDB id-3PP0) targeting breast cancer using Schrodinger suit-2016-2, Maestro 9.6 version. Docking against HER2 was performed using Glide module, Insilco ADMET screening by qikprop module and free binding energy by Prime- MMGBSA module. The binding affinity of the molecules towards HER2 was selected by GLIDE score and interaction patterns. Many compounds showed strong hydrophobic interactions and hydrogen bonding interactions to inhibit HER2. The compounds 1a-x have good binding affinity with Glide scores -6.6 to -9.7 when compared with standards ledacrine(-6.3) and tamoxifen(-3.7). The ADMET properties are within recommended values. MM-GBSA binding results of the most potent inhibitor are favourable. The compounds, 1o,f,n,d,m,w with good Glide scores may produce significant anti-breast cancer activity and further in-vitro and in-vivo investigations.
{"title":"Molecular docking, in-silico ADMET screening, MM-GBSA binding free energy of some novel isoxazole substituted 9-amnoacridines as HER2 inhibitors targetting breast cancer","authors":"R. Kalirajan, A. Pandiselvi, B. Gowramma","doi":"10.1504/ijcbdd.2020.10029437","DOIUrl":"https://doi.org/10.1504/ijcbdd.2020.10029437","url":null,"abstract":"9-Aminoacridines are known DNA-intercalating agents, due to antiproliferative properties. Anticancer agents with 9-aminoacridines like amascrine, and nitracrine were developed. Docking studies were performed for isoxazole substituted 9-aminoacridines 1a-x as selective HER2 inhibitors (PDB id-3PP0) targeting breast cancer using Schrodinger suit-2016-2, Maestro 9.6 version. Docking against HER2 was performed using Glide module, Insilco ADMET screening by qikprop module and free binding energy by Prime- MMGBSA module. The binding affinity of the molecules towards HER2 was selected by GLIDE score and interaction patterns. Many compounds showed strong hydrophobic interactions and hydrogen bonding interactions to inhibit HER2. The compounds 1a-x have good binding affinity with Glide scores -6.6 to -9.7 when compared with standards ledacrine(-6.3) and tamoxifen(-3.7). The ADMET properties are within recommended values. MM-GBSA binding results of the most potent inhibitor are favourable. The compounds, 1o,f,n,d,m,w with good Glide scores may produce significant anti-breast cancer activity and further in-vitro and in-vivo investigations.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"53 1","pages":"155-168"},"PeriodicalIF":0.0,"publicationDate":"2020-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86040672","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}
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