B. Milićević, M. Ivanovic, B. Stojanovic, N. Filipovic
Biophysical muscle models, often called Huxley-type models, are based on the underlying physiology of muscles, making them suitable for modeling non-uniform and unsteady contractions. This kind of model can be computationally intensive, which makes the usage of large-scale simulations difficult. To enable more efficient usage of the Huxley muscle model, we created a data-driven surrogate model, which behaves similarly to the original Huxley muscle model, but it requires significantly less computational power. From several numerical simulations, we acquired a lot of data and trained deep neural networks so that the behavior of the neural network resembles the behavior of the Huxley model. Since muscle models are history-dependent we used time series as an input and we trained a recurrent neural network to produce stress and instantaneous stiffness. The real challenge was to get the neural network to predict these values precisely enough for the numerical simulation to work properly and produce accurate results. In our work, we showed results obtained with the original Huxley model and surrogate Huxley model for several muscle twitch contractions. Based on similarities between the surrogate model and the original model we can conclude that the surrogate has the potential to replace the original model within numerical simulations.
{"title":"HUXLEY SURROGATE MODEL FOR TWITCH MUSCLE CONTRACTION","authors":"B. Milićević, M. Ivanovic, B. Stojanovic, N. Filipovic","doi":"10.46793/iccbi21.239m","DOIUrl":"https://doi.org/10.46793/iccbi21.239m","url":null,"abstract":"Biophysical muscle models, often called Huxley-type models, are based on the underlying physiology of muscles, making them suitable for modeling non-uniform and unsteady contractions. This kind of model can be computationally intensive, which makes the usage of large-scale simulations difficult. To enable more efficient usage of the Huxley muscle model, we created a data-driven surrogate model, which behaves similarly to the original Huxley muscle model, but it requires significantly less computational power. From several numerical simulations, we acquired a lot of data and trained deep neural networks so that the behavior of the neural network resembles the behavior of the Huxley model. Since muscle models are history-dependent we used time series as an input and we trained a recurrent neural network to produce stress and instantaneous stiffness. The real challenge was to get the neural network to predict these values precisely enough for the numerical simulation to work properly and produce accurate results. In our work, we showed results obtained with the original Huxley model and surrogate Huxley model for several muscle twitch contractions. Based on similarities between the surrogate model and the original model we can conclude that the surrogate has the potential to replace the original model within numerical simulations.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89603082","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}
Discovery of the antitumor activity of platinum complex, cisplatin, cis-Pt(NH3)2Cl2, and later carboplatin and oxaliplatin, led to the intensive investigation of the potential antitumor activity of the huge number of platinum complexes. Furthermore, it is well-known that platinum complexes express toxicity, numerous side effects and resistance, so the scientists make a lot of efforts to synthetize, beside Pt(II) and Pt(IV), other non-platinum compounds with potential antitumor activity, such as Pd(II), Ru(II/III) and Au(III) complexes. The goal of this study is to summarize the results of the investigation of the interactions between some mononuclear, homo- and hetero-polynuclear Pt(II), Pd(II), Ru(II/III) and Au(III) complexes with different sulfur- and nitrogen-donor biologically relevant nucleophiles. Among mononuclear complexes, the compounds with aromatic terpy (tepyridine) or bpma (bis-(2- pyridylmethyl)amine) and aliphatic dien (diethylentriamine) nitrogen-containing inert ligands were studied. Different homo- and hetero-polynuclear complexes with pz (pyrazine) or 4,4’-bipy (4,4’- bipyridine) as bridging and mostly en (ethylenediamine), bipy (2,2’-bipyridine) and dach (trans-1,2- diaminocyclohexane) as inert ligands were studied as well. The research was focused on the connection between the structure and the mechanisms of interactions with different biomolecules, such as L- cysteine (L-Cys), L-methionine (L-Met), tripeptide glutathione (GSH), guanosine-5’-monophosphate (5’-GMP), DNA and bovine serum albumin (BSA). Some of these complexes were selected for in vitro studies of the cytotoxicity on different tumor cell lines. Observed results contribute a lot as a guidance for the future design and determination of the structure-activity relationship (SAR) of different transition metal ion complexes.
{"title":"TRANSITION METAL ION COMPLEXES AS POTENTIAL ANTITUMOR AGENTS","authors":"B. Petrović","doi":"10.46793/iccbi21.009p","DOIUrl":"https://doi.org/10.46793/iccbi21.009p","url":null,"abstract":"Discovery of the antitumor activity of platinum complex, cisplatin, cis-Pt(NH3)2Cl2, and later carboplatin and oxaliplatin, led to the intensive investigation of the potential antitumor activity of the huge number of platinum complexes. Furthermore, it is well-known that platinum complexes express toxicity, numerous side effects and resistance, so the scientists make a lot of efforts to synthetize, beside Pt(II) and Pt(IV), other non-platinum compounds with potential antitumor activity, such as Pd(II), Ru(II/III) and Au(III) complexes. The goal of this study is to summarize the results of the investigation of the interactions between some mononuclear, homo- and hetero-polynuclear Pt(II), Pd(II), Ru(II/III) and Au(III) complexes with different sulfur- and nitrogen-donor biologically relevant nucleophiles. Among mononuclear complexes, the compounds with aromatic terpy (tepyridine) or bpma (bis-(2- pyridylmethyl)amine) and aliphatic dien (diethylentriamine) nitrogen-containing inert ligands were studied. Different homo- and hetero-polynuclear complexes with pz (pyrazine) or 4,4’-bipy (4,4’- bipyridine) as bridging and mostly en (ethylenediamine), bipy (2,2’-bipyridine) and dach (trans-1,2- diaminocyclohexane) as inert ligands were studied as well. The research was focused on the connection between the structure and the mechanisms of interactions with different biomolecules, such as L- cysteine (L-Cys), L-methionine (L-Met), tripeptide glutathione (GSH), guanosine-5’-monophosphate (5’-GMP), DNA and bovine serum albumin (BSA). Some of these complexes were selected for in vitro studies of the cytotoxicity on different tumor cell lines. Observed results contribute a lot as a guidance for the future design and determination of the structure-activity relationship (SAR) of different transition metal ion complexes.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73154246","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}
M. Stanković, Jelena Z. Pribojac, Jelena N. Terzić, O. Stefanović
Mentha piperita and Melissa officinalis are both well-known medicinal plants that have applications in traditional medicine. In this research the antibacterial activity of the ethanol extracts of M. piperita and M. officinalis was examined against 14 bacterial strains via the microdilution method. Minimum inhibitory concentrations of ethanol extracts of both plant species ranged from 0.312 to 20 mg/mL. Standard strains of Staphylococcus aureus ATCC 25923 at a concentration of 0.312 mg/mL and Bacillus subtilis ATCC 6633 at a concentration of 1.25 mg/mL showed the highest sensitivity to the ethanol extract of M. piperita. Ethanol extract of M. officinalis showed antibacterial activity on standard strains of S. aureus ATCC 25923 and B. subtilis ATCC 6633 at a concentration of 0.625 mg/mL. In addition to the mentioned standard strains, it showed activity on the isolate from the food Proteus spp. at a concentration of 0.312 mg/mL and isolate from the wound Proteus mirabilis at a concentration of 0.625 mg/mL. Mechanism of action of the ethanol extract of M. officinalis was examined on the permeability of the bacterial cell membrane. The effect of the extract on the increased permeability of the cell membrane was measured based on the release of proteins and the percentage of crystal violet binding. Ethanol extract of M. officinalis has been shown to act at the level of the cell membrane in the following bacterial strains of Pseudomonas aeruginosa, S. aureus and Enterococcus spp.
{"title":"EFFECT OF PLANT EXTRACTS ON BACTERIAL GROWTH AND POTENTIAL MECHANISM OF ACTION","authors":"M. Stanković, Jelena Z. Pribojac, Jelena N. Terzić, O. Stefanović","doi":"10.46793/iccbi21.343s","DOIUrl":"https://doi.org/10.46793/iccbi21.343s","url":null,"abstract":"Mentha piperita and Melissa officinalis are both well-known medicinal plants that have applications in traditional medicine. In this research the antibacterial activity of the ethanol extracts of M. piperita and M. officinalis was examined against 14 bacterial strains via the microdilution method. Minimum inhibitory concentrations of ethanol extracts of both plant species ranged from 0.312 to 20 mg/mL. Standard strains of Staphylococcus aureus ATCC 25923 at a concentration of 0.312 mg/mL and Bacillus subtilis ATCC 6633 at a concentration of 1.25 mg/mL showed the highest sensitivity to the ethanol extract of M. piperita. Ethanol extract of M. officinalis showed antibacterial activity on standard strains of S. aureus ATCC 25923 and B. subtilis ATCC 6633 at a concentration of 0.625 mg/mL. In addition to the mentioned standard strains, it showed activity on the isolate from the food Proteus spp. at a concentration of 0.312 mg/mL and isolate from the wound Proteus mirabilis at a concentration of 0.625 mg/mL. Mechanism of action of the ethanol extract of M. officinalis was examined on the permeability of the bacterial cell membrane. The effect of the extract on the increased permeability of the cell membrane was measured based on the release of proteins and the percentage of crystal violet binding. Ethanol extract of M. officinalis has been shown to act at the level of the cell membrane in the following bacterial strains of Pseudomonas aeruginosa, S. aureus and Enterococcus spp.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76932121","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}
Cytochrome P450 17A1 (CYP17A1) is a critically important enzyme in humans that catalyzes the formation of all endogenous androgens. This enzyme is often considered a molecular target for the development of novel high efficient drugs against prostate cancer. In the present work, the random forest algorithm was used to conduct a QSAR study on 370 CYP17A1 ligands with different structures that were collected from the literature and databases, and a QSAR model was created based on the five important descriptors screened out – 2D adjacency and distance matrix descriptors, 2D atom counts and bond counts and 3D surface area, volume and shape descriptors. The model was verified by the test set (accuracy, specificity, sensitivity, F-measure, MCC, and AUC were calculated). It was revealed that the hydrophobic properties of the vdW surface of the ligand have a significant contribution to the activity prediction. The hydrophobic effect of the molecules may be aroused by the presence of the hydrophobic groups or aromatic rings in the molecules. The created QSAR model shows that the molecules with more aromatic rings have better activity. The accuracy of the model on the test set was 84%, precision – 81%, sensitivity – 93%, specificity – 72%, F-measure – 0.87, MCC – 0.67, AUC – 0.88. The model has good robustness and predictive ability and can be used to screen and discover new highly active CYP17A1 inhibitors.
{"title":"THE EXPLORATION OF CYP17A1 LIGAND SPACE BY THE QSAR MODEL","authors":"N. Boboriko, He Liying, Yaraslau U Dzichenka","doi":"10.46793/iccbi21.439b","DOIUrl":"https://doi.org/10.46793/iccbi21.439b","url":null,"abstract":"Cytochrome P450 17A1 (CYP17A1) is a critically important enzyme in humans that catalyzes the formation of all endogenous androgens. This enzyme is often considered a molecular target for the development of novel high efficient drugs against prostate cancer. In the present work, the random forest algorithm was used to conduct a QSAR study on 370 CYP17A1 ligands with different structures that were collected from the literature and databases, and a QSAR model was created based on the five important descriptors screened out – 2D adjacency and distance matrix descriptors, 2D atom counts and bond counts and 3D surface area, volume and shape descriptors. The model was verified by the test set (accuracy, specificity, sensitivity, F-measure, MCC, and AUC were calculated). It was revealed that the hydrophobic properties of the vdW surface of the ligand have a significant contribution to the activity prediction. The hydrophobic effect of the molecules may be aroused by the presence of the hydrophobic groups or aromatic rings in the molecules. The created QSAR model shows that the molecules with more aromatic rings have better activity. The accuracy of the model on the test set was 84%, precision – 81%, sensitivity – 93%, specificity – 72%, F-measure – 0.87, MCC – 0.67, AUC – 0.88. The model has good robustness and predictive ability and can be used to screen and discover new highly active CYP17A1 inhibitors.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91075667","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}
M. Markovic, V. Panic, Julijana D. Tadić, R. Pjanovic
Targeted drug delivery is powerful tool which researchers use to achieve safer and more efficient therapy of many diseases, including various types of cancer. Many chemotherapeutics are poorly water- soluble, so their encapsulation and targeted delivery remain quite challenge. Hydrogels based on poly(methacrylic acid) (PMAA) are widely investigated for targeted drug delivery due to their pH sensitivity, non-toxicity and biocompatibility. Still, due to the PMAA highly hydrophilic nature, PMAA can only be used for encapsulation and targeted delivery of water-soluble drugs. Our previous research was directed towards overcoming this limitation: PMAA was modified with amphiphilic protein – casein and poorly-water soluble model drug – caffeine – was encapsulated (PMAC). Present study is focused on investigation how variation of amount of one of the most important hydrogels network parameter such as crosslinker affect PMAC swelling properties and caffeine release. The group of hybrid hydrogels – PMAC – was synthesized with various amount of crosslinker: 0.4mol%, 0.8mol%, 1.6mol% and 3.2mol% with respect to methacrylic acid. Swelling behavior of hybrid hydrogels and caffeine release was investigated in two environments which simulated human stomach and intestines. Obtained results showed that targeted delivery of poorly water-soluble model drug was achieved and that its release can be prolonged up to 24h. Also, kinetic of poorly water-soluble drug release can be easily modified only by changing crosslinker amount. PMAC hybrid hydrogels have huge potential for targeted delivery of poorly water-soluble active substances.
{"title":"EFFECT OF CROSSLINKER AMOUNT ON HYBRID HYDROGELS SWELLING AND DRUG RELEASE","authors":"M. Markovic, V. Panic, Julijana D. Tadić, R. Pjanovic","doi":"10.46793/iccbi21.125m","DOIUrl":"https://doi.org/10.46793/iccbi21.125m","url":null,"abstract":"Targeted drug delivery is powerful tool which researchers use to achieve safer and more efficient therapy of many diseases, including various types of cancer. Many chemotherapeutics are poorly water- soluble, so their encapsulation and targeted delivery remain quite challenge. Hydrogels based on poly(methacrylic acid) (PMAA) are widely investigated for targeted drug delivery due to their pH sensitivity, non-toxicity and biocompatibility. Still, due to the PMAA highly hydrophilic nature, PMAA can only be used for encapsulation and targeted delivery of water-soluble drugs. Our previous research was directed towards overcoming this limitation: PMAA was modified with amphiphilic protein – casein and poorly-water soluble model drug – caffeine – was encapsulated (PMAC). Present study is focused on investigation how variation of amount of one of the most important hydrogels network parameter such as crosslinker affect PMAC swelling properties and caffeine release. The group of hybrid hydrogels – PMAC – was synthesized with various amount of crosslinker: 0.4mol%, 0.8mol%, 1.6mol% and 3.2mol% with respect to methacrylic acid. Swelling behavior of hybrid hydrogels and caffeine release was investigated in two environments which simulated human stomach and intestines. Obtained results showed that targeted delivery of poorly water-soluble model drug was achieved and that its release can be prolonged up to 24h. Also, kinetic of poorly water-soluble drug release can be easily modified only by changing crosslinker amount. PMAC hybrid hydrogels have huge potential for targeted delivery of poorly water-soluble active substances.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78083594","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}
Dušica M Simijonović, M. Antonijević, Edina H. Avdović, Z. Petrović, Z. Marković
The protein that controls cell differentiation in acute myeloid leukemia is MCL-1. High-level of this protein causes the carcinogenesis. In this paper inhibitory effect of two coumarin benzoylhydrazones,(E)-2-hydroxy-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (A) and (E)-4-hydroxy-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (B) against MCL-1 protein was investigated. For this purpose, a molecular docking simulations were used. The obtained results showed that compound A showed better activity than compound B. Also, the docking simulations against MCL-1 protein were performed for melphalan or (2S)-2-amino- 3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid and two 4-chlorocoumarin benzoylhydrazone derivatives, N′-[(E)-(4-chloro-2-oxo-2H-chromen-3-yl)- methylidene]benzohydrazide (4a) and N′-[(E)-(4-chloro-2-oxo-2H-chromen-3-yl)- methylidene]-4-hydroxybenzohydrazide (4b). In this study, melphalan as a chemotherapy drug commonly used in treating multiple myeloma and compounds 4a and 4b as structurally similar compounds with A and B were used as reference compounds. It was shown that these reference compounds exhibited similar activity as compound B. In addition, the potential toxicology of compounds A and B, as well as reference compounds was determined by the ProTox-II webserver. The results revealed that compounds A and B are 3 to 5 times lower toxic than reference compounds.
{"title":"INHIBITORY EFFECT OF COUMARIN BENZOYLHYDRAZONES ON MCL-1 PROTEIN","authors":"Dušica M Simijonović, M. Antonijević, Edina H. Avdović, Z. Petrović, Z. Marković","doi":"10.46793/iccbi21.442s","DOIUrl":"https://doi.org/10.46793/iccbi21.442s","url":null,"abstract":"The protein that controls cell differentiation in acute myeloid leukemia is MCL-1. High-level of this protein causes the carcinogenesis. In this paper inhibitory effect of two coumarin benzoylhydrazones,(E)-2-hydroxy-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (A) and (E)-4-hydroxy-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (B) against MCL-1 protein was investigated. For this purpose, a molecular docking simulations were used. The obtained results showed that compound A showed better activity than compound B. Also, the docking simulations against MCL-1 protein were performed for melphalan or (2S)-2-amino- 3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid and two 4-chlorocoumarin benzoylhydrazone derivatives, N′-[(E)-(4-chloro-2-oxo-2H-chromen-3-yl)- methylidene]benzohydrazide (4a) and N′-[(E)-(4-chloro-2-oxo-2H-chromen-3-yl)- methylidene]-4-hydroxybenzohydrazide (4b). In this study, melphalan as a chemotherapy drug commonly used in treating multiple myeloma and compounds 4a and 4b as structurally similar compounds with A and B were used as reference compounds. It was shown that these reference compounds exhibited similar activity as compound B. In addition, the potential toxicology of compounds A and B, as well as reference compounds was determined by the ProTox-II webserver. The results revealed that compounds A and B are 3 to 5 times lower toxic than reference compounds.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"431 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77813477","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}
M. Vraneš, J. Panić, S. Papović, Teodora Teona Borović, A. Tot, Nikolet Baganj, S. Gadžurić
In this work, the absorption spectra of cobalt(II) nitrate and bromide complexes in the composition 0.3Ca(NO3)2 – 0.7NH4NO3 – H2O have been investigated in the 400-800 nm range of wavelength at T = 328.15 K and atmospheric pressure P = 101.3 kPa. Spectra were recorded in solutions with variable water content (R = H2O/salt mole ratio; R = 1.0, 1.2 and 1.6). The blue shift of the absorption maximum with the water content increase (R) suggest simultaneous coordination by water molecules and nitrate ions. From an analysis of the spectra, it can be concluded that the following: [Co(NO3)4(H2O)2]2−, [Co(NO3)2Br2]2− and [CoBr4]2− complexes were formed. The overall stability constants of these complexes species spectra were calculated at T = 328.15 K.
{"title":"SPECTROPHOTOMETRIC INVESTIGATION OF COBALT BROMIDE COMPLEX FORMATION IN AQUEOUS CALCIUM NITRATE– AMMONIUM NITRATE MELTS AT T = 328.15 K. INFLUENCE OF WATER CONTENT","authors":"M. Vraneš, J. Panić, S. Papović, Teodora Teona Borović, A. Tot, Nikolet Baganj, S. Gadžurić","doi":"10.46793/iccbi21.454v","DOIUrl":"https://doi.org/10.46793/iccbi21.454v","url":null,"abstract":"In this work, the absorption spectra of cobalt(II) nitrate and bromide complexes in the composition 0.3Ca(NO3)2 – 0.7NH4NO3 – H2O have been investigated in the 400-800 nm range of wavelength at T = 328.15 K and atmospheric pressure P = 101.3 kPa. Spectra were recorded in solutions with variable water content (R = H2O/salt mole ratio; R = 1.0, 1.2 and 1.6). The blue shift of the absorption maximum with the water content increase (R) suggest simultaneous coordination by water molecules and nitrate ions. From an analysis of the spectra, it can be concluded that the following: [Co(NO3)4(H2O)2]2−, [Co(NO3)2Br2]2− and [CoBr4]2− complexes were formed. The overall stability constants of these complexes species spectra were calculated at T = 328.15 K.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88069880","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}
S. Jeremic, Jelena R. Đorović Jovanović, Marijana Stanojević Pirković, Z. Marković
The operative mechanism of the antioxidative action of 1,2,4-trihydroxythioxanthone (TX) is investigated in this contribution. Conclusions are made based on enthalpy values, as thermodynamical parameters. All calculations are done using the M06-2X/6-311++G(d,p) level of theory. To imitate polar and non-polar environments, calculations are done in water and benzene as the medium. It is found that, among three possible radicals that TX can generate, the most stable is the one obtained by homolytic cleavage of the O-H group in position 4. It was found that HAT (Hydrogen Atom Transfer) is the most plausible mechanism for that purpose in benzene. On the other hand, the most favorable mechanism in water is SPLET (Sequential Proton Loss Electron Transfer). Here is estimated the capacity of TX to deactivate hydroxyl (HO●), hydroperoxyl (HOO●) and methylperoxyl radical (CH3OO●). It is found that TX can deactivate all three free radicals following HAT and SPLET reaction mechanisms competitively, in the polar and non-polar environment. SET-PT (Single-Electron Transfer followed by Proton Transfer) is the inoperative mechanism for radicals scavenging, in the polar and non-polar environment.
{"title":"THERMODYNAMICALLY INVESTIGATIONS OF FREE RADICAL SCAVENGER POTENCY OF 1,2,4-TRIHYDROXYTHIOXANTHONE","authors":"S. Jeremic, Jelena R. Đorović Jovanović, Marijana Stanojević Pirković, Z. Marković","doi":"10.46793/iccbi21.414j","DOIUrl":"https://doi.org/10.46793/iccbi21.414j","url":null,"abstract":"The operative mechanism of the antioxidative action of 1,2,4-trihydroxythioxanthone (TX) is investigated in this contribution. Conclusions are made based on enthalpy values, as thermodynamical parameters. All calculations are done using the M06-2X/6-311++G(d,p) level of theory. To imitate polar and non-polar environments, calculations are done in water and benzene as the medium. It is found that, among three possible radicals that TX can generate, the most stable is the one obtained by homolytic cleavage of the O-H group in position 4. It was found that HAT (Hydrogen Atom Transfer) is the most plausible mechanism for that purpose in benzene. On the other hand, the most favorable mechanism in water is SPLET (Sequential Proton Loss Electron Transfer). Here is estimated the capacity of TX to deactivate hydroxyl (HO●), hydroperoxyl (HOO●) and methylperoxyl radical (CH3OO●). It is found that TX can deactivate all three free radicals following HAT and SPLET reaction mechanisms competitively, in the polar and non-polar environment. SET-PT (Single-Electron Transfer followed by Proton Transfer) is the inoperative mechanism for radicals scavenging, in the polar and non-polar environment.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85346116","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}
N. Nedeljković, V. Dobričić, M. Mijajlovic, G. Radić, M. Nikolic, A. Stanković, Z. Vujić
Masking the carboxyl group of naproxen with other functional groups may be a promising strategy to decrease its gastrointestinal toxicity. Thiourea moiety has been described as an important pharmacophore in a variety of pharmacologically active compounds, including anti-inflammatory, antiviral, anticancer, hypoglycemic and antimicrobial agents. Our research group has previously designed twenty novel thiourea derivatives of naproxen, containing amino acids (glycine, L-alanine, β-alanine, L-valine and L-phenylalanine – compounds 1,2,3,4 and 5, respectively), their methyl (6–10) and ethyl esters (11–15), as well as aromatic amines (16–20). Pharmacokinetic properties and druglikeness of these compounds were predicted using SwissADME web tool (http://www.swissadme.ch/). Predicted pharmacokinetic properties include potential for gastrointestinal absorption, blood-brain barrier permeability, skin permeability, transport mediated by P-glycoproteins and enzyme inhibitory potential. Druglikeness was evaluated using Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules, as well as on the basis of bioavailability score. All tested compounds had high-predicted gastrointestinal absorption and low blood-brain barrier permeability. Also, derivatives 2, 4, 7, 9, 10, 12, 14, 15 and 18 were predicted to be substrates for P-glycoprotein. Derivatives with aromatic amines (16–20) showed inhibitory potential against all tested CYP isoforms. Derivative 19 had the highest, while derivative 13 demonstrated the lowest predicted skin permeability. Finally, derivatives 1–12, except 5 and 10, have druglike structures, since they obey to all imposed rules.
{"title":"„IN SILICO“ PREDICTION OF PHARMACOKINETIC PROPERTIES AND DRUGLIKENESS OF NOVEL THIOUREA DERIVATIVES OF NAPROXEN","authors":"N. Nedeljković, V. Dobričić, M. Mijajlovic, G. Radić, M. Nikolic, A. Stanković, Z. Vujić","doi":"10.46793/iccbi21.371n","DOIUrl":"https://doi.org/10.46793/iccbi21.371n","url":null,"abstract":"Masking the carboxyl group of naproxen with other functional groups may be a promising strategy to decrease its gastrointestinal toxicity. Thiourea moiety has been described as an important pharmacophore in a variety of pharmacologically active compounds, including anti-inflammatory, antiviral, anticancer, hypoglycemic and antimicrobial agents. Our research group has previously designed twenty novel thiourea derivatives of naproxen, containing amino acids (glycine, L-alanine, β-alanine, L-valine and L-phenylalanine – compounds 1,2,3,4 and 5, respectively), their methyl (6–10) and ethyl esters (11–15), as well as aromatic amines (16–20). Pharmacokinetic properties and druglikeness of these compounds were predicted using SwissADME web tool (http://www.swissadme.ch/). Predicted pharmacokinetic properties include potential for gastrointestinal absorption, blood-brain barrier permeability, skin permeability, transport mediated by P-glycoproteins and enzyme inhibitory potential. Druglikeness was evaluated using Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules, as well as on the basis of bioavailability score. All tested compounds had high-predicted gastrointestinal absorption and low blood-brain barrier permeability. Also, derivatives 2, 4, 7, 9, 10, 12, 14, 15 and 18 were predicted to be substrates for P-glycoprotein. Derivatives with aromatic amines (16–20) showed inhibitory potential against all tested CYP isoforms. Derivative 19 had the highest, while derivative 13 demonstrated the lowest predicted skin permeability. Finally, derivatives 1–12, except 5 and 10, have druglike structures, since they obey to all imposed rules.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82715295","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}
Biljana M Šmit, Asija Halilagić, Enisa Selimović, Jelena Katanić Stanković, N. Srećković, T. Soldatović
New dinuclear Zn(II)-L-Cu(II) complexes with different bridging ligands were synthesized. Interactions of these complexes with biologically important nucleophiles, 5′-GMP, 5′-IMP and GSH, were investigated by Uv-Vis spectrofotometric method. The distances between the metal ions lead to less reactivity of both centers due to reduced electronic communication between them and an increasing of electron density on the metal centers itself. Both complexes showed moderate antimicrobial activity against most of the tested bacterial and fungal strains.
{"title":"STUDIES OF SUBSTITUTION REACTIONS WITH IMPORTANT BIOMOLECULES AND ANTIMICROBIAL ACTIVITY OF NOVEL ZN(II)-L-CU(II) COMPLEXES","authors":"Biljana M Šmit, Asija Halilagić, Enisa Selimović, Jelena Katanić Stanković, N. Srećković, T. Soldatović","doi":"10.46793/iccbi21.328s","DOIUrl":"https://doi.org/10.46793/iccbi21.328s","url":null,"abstract":"New dinuclear Zn(II)-L-Cu(II) complexes with different bridging ligands were synthesized. Interactions of these complexes with biologically important nucleophiles, 5′-GMP, 5′-IMP and GSH, were investigated by Uv-Vis spectrofotometric method. The distances between the metal ions lead to less reactivity of both centers due to reduced electronic communication between them and an increasing of electron density on the metal centers itself. Both complexes showed moderate antimicrobial activity against most of the tested bacterial and fungal strains.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82845282","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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