Micromeria (Bentham, 1829.) is a polymorph genus of Lamiaceae with about 130 species grouped in three sections: Cymularia, Eumicromeria and Pseudomelissa, the most diverse in Mediterranean regions, but widespread across Europe, Asia, Africa, and North America [1]. Up to now, eight Micromeria species have been recorded inhabiting the territory of Montenegro including a dwarf shrub, Micromeria juliana (L.) Benth. Knowing the existence of the variability in quantity and qualitative makeup, interpopulational, and the interspecies variability of the up to now reported essential oils from this plant prompted us to make the detailed analysis of the M. juliana specimens originating from rocky, sunny carbonate rock bases in Zabrđe, Montenegro, since the plant material from this area was not examined before. Detailed GC-MS analysis of the obtained essential oil resulted in 70 identified components among which α-pinene (12.2%), (E)-nerolidol (8.9%), viridiflorol (6.8%), limonene (6.1%), and borneol (5.2%) prevailed, differing significantly in content from the previously reported populations (Morača canyon, Cijevna canyon, Mt. Orjen and Mt. Krivošije) [2]. The objective of this study is to gain insight into the essential oil structure, determine the possible mutual similarity and the variability in their chemical compositions, and to enclose possible diversity in the secondary metabolite profile dependent on the site of collection.
{"title":"ESSENTIAL OIL ANALYSIS OF THE „MICROMERIA JULIANA“ (L.) BENTH., FROM LUŠTICA, MONTENEGRO","authors":"S. Filipović, N. Radulović","doi":"10.46793/iccbi21.332f","DOIUrl":"https://doi.org/10.46793/iccbi21.332f","url":null,"abstract":"Micromeria (Bentham, 1829.) is a polymorph genus of Lamiaceae with about 130 species grouped in three sections: Cymularia, Eumicromeria and Pseudomelissa, the most diverse in Mediterranean regions, but widespread across Europe, Asia, Africa, and North America [1]. Up to now, eight Micromeria species have been recorded inhabiting the territory of Montenegro including a dwarf shrub, Micromeria juliana (L.) Benth. Knowing the existence of the variability in quantity and qualitative makeup, interpopulational, and the interspecies variability of the up to now reported essential oils from this plant prompted us to make the detailed analysis of the M. juliana specimens originating from rocky, sunny carbonate rock bases in Zabrđe, Montenegro, since the plant material from this area was not examined before. Detailed GC-MS analysis of the obtained essential oil resulted in 70 identified components among which α-pinene (12.2%), (E)-nerolidol (8.9%), viridiflorol (6.8%), limonene (6.1%), and borneol (5.2%) prevailed, differing significantly in content from the previously reported populations (Morača canyon, Cijevna canyon, Mt. Orjen and Mt. Krivošije) [2]. The objective of this study is to gain insight into the essential oil structure, determine the possible mutual similarity and the variability in their chemical compositions, and to enclose possible diversity in the secondary metabolite profile dependent on the site of collection.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85226812","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}
Ilija N. Cvijetić, Petar M. Ristivojević, Maja Krstić-Ristivojević, D. Milojković-Opsenica
Tyrosinase is an enzyme involved in generation of dopamine-quinones, which has an important role in oxidative stress associated with the Parkinson’s disease. It is also a common molecular target for the design of novel anti-melanogenic agents. The inhibition of tyrosinase might be responsible for the experimentally observed intracellular antioxidant activity of α-arbutin. Moreover, intrinsic radical scavenging capacity of α-arbutin should also be considered. The binding mode of α-arbutin into the active site of Bacillus megaterium tyrosinase is predicted using AutoDock Vina 1.1. To map the thermodynamic feasibility of HAT and SET-PT mechanisms of the intrinsic antioxidant capacity α-arbutin, bond dissociation enthalpies (BDEs) and ionization potential (IP) are calculated using DFT with B3LYP functional and 6-31+g(d,p) basis set. α-Arbutin fitted well into the active site of tyrosinase, with the calculated binding affinity of -17.5 kcal/mol. The phenolic moiety is located deep into the binding pocket, interacting with His residues around Cu2+ ion. The binding mode of α-arbutin is stabilized via HBD interactions with His231, His42, His60, Arg209, Gly216, and Asn205, HBA interaction with Arg209 at the outer part of active site, and hydrophobic interactions with His208, Val218 and Ala221. The calculated IP of α-arbutin is 175.18 kcal/mol, and BDE of phenolic group is 79.85 kcal/mol. The spin densities of radical-cation and hydroxyl radical are delocalized on the aglycone moiety. The results of this study provide valuable structural insights into the molecular mechanisms of biological action of α-arbutin, and might be exploited for the design of more potent analogues.
{"title":"EXPLORING THE POTENTIAL OF Α-ARBUTIN AS THE INHIBITOR OF NEURODEGENERATIVE DISORDERS","authors":"Ilija N. Cvijetić, Petar M. Ristivojević, Maja Krstić-Ristivojević, D. Milojković-Opsenica","doi":"10.46793/iccbi21.292c","DOIUrl":"https://doi.org/10.46793/iccbi21.292c","url":null,"abstract":"Tyrosinase is an enzyme involved in generation of dopamine-quinones, which has an important role in oxidative stress associated with the Parkinson’s disease. It is also a common molecular target for the design of novel anti-melanogenic agents. The inhibition of tyrosinase might be responsible for the experimentally observed intracellular antioxidant activity of α-arbutin. Moreover, intrinsic radical scavenging capacity of α-arbutin should also be considered. The binding mode of α-arbutin into the active site of Bacillus megaterium tyrosinase is predicted using AutoDock Vina 1.1. To map the thermodynamic feasibility of HAT and SET-PT mechanisms of the intrinsic antioxidant capacity α-arbutin, bond dissociation enthalpies (BDEs) and ionization potential (IP) are calculated using DFT with B3LYP functional and 6-31+g(d,p) basis set. α-Arbutin fitted well into the active site of tyrosinase, with the calculated binding affinity of -17.5 kcal/mol. The phenolic moiety is located deep into the binding pocket, interacting with His residues around Cu2+ ion. The binding mode of α-arbutin is stabilized via HBD interactions with His231, His42, His60, Arg209, Gly216, and Asn205, HBA interaction with Arg209 at the outer part of active site, and hydrophobic interactions with His208, Val218 and Ala221. The calculated IP of α-arbutin is 175.18 kcal/mol, and BDE of phenolic group is 79.85 kcal/mol. The spin densities of radical-cation and hydroxyl radical are delocalized on the aglycone moiety. The results of this study provide valuable structural insights into the molecular mechanisms of biological action of α-arbutin, and might be exploited for the design of more potent analogues.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91008164","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}
Katarina Virijević, Jelica Grujić, Milena Jovanović, Nikolina Kastratović, Ana Mirić, D. Nikolić, M. Zivanovic, N. Filipovic
Electrospinning is highly used technique in the tissue engineering field, particularly in biomedical application [1]. The constricted concepts of this process are based on generate nonwoven nanofibers. The method involves high voltage electricity which is applied to the liquid solution and a collector, which lets the solution force out from a nozzle forming a jet. The jet formed fibers under influence of electrostatic forces concentrated and deposited these on the collector. Main objective of this study was to fabricate gelatin scaffolds with micro/nano-scale for successful wound dressing. Gelatin can mimic the chemical composition, physical structure and structure of the native skin extracellular matrix (ECM). However, the first and main principle in this study is the optimization of parameters of the electrospinning process. The used parameters have a crucial role in obtaining suitable fibers for further cell seeding and cell growth in vitro. With the use of series of various biocompatible polymers and solvents, solutions were tested in various electrospinning settings in order to produce microscale fibers. The scaffolds were analysed with scanning electron microscope images for fiber diameter measurement.
{"title":"ELECTROSPUN GELATIN NANOFIBROUS SCAFFOLDS – APPLICATIONS IN TISSUE ENGINEERING","authors":"Katarina Virijević, Jelica Grujić, Milena Jovanović, Nikolina Kastratović, Ana Mirić, D. Nikolić, M. Zivanovic, N. Filipovic","doi":"10.46793/iccbi21.251v","DOIUrl":"https://doi.org/10.46793/iccbi21.251v","url":null,"abstract":"Electrospinning is highly used technique in the tissue engineering field, particularly in biomedical application [1]. The constricted concepts of this process are based on generate nonwoven nanofibers. The method involves high voltage electricity which is applied to the liquid solution and a collector, which lets the solution force out from a nozzle forming a jet. The jet formed fibers under influence of electrostatic forces concentrated and deposited these on the collector. Main objective of this study was to fabricate gelatin scaffolds with micro/nano-scale for successful wound dressing. Gelatin can mimic the chemical composition, physical structure and structure of the native skin extracellular matrix (ECM). However, the first and main principle in this study is the optimization of parameters of the electrospinning process. The used parameters have a crucial role in obtaining suitable fibers for further cell seeding and cell growth in vitro. With the use of series of various biocompatible polymers and solvents, solutions were tested in various electrospinning settings in order to produce microscale fibers. The scaffolds were analysed with scanning electron microscope images for fiber diameter measurement.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89870474","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}
Julijana Blagojević, Olga M. Govedarica, Kojić Predrag, O. Bera, M. Jovičić, Sonja Stojanov, J. Pavličević, Dragan D. Govedarica
Good selection of natural rubber compounds is substantial in rubber industry. Behavior of products based on natural rubber is determined by rubber blending components, especially nature of process oil and concentration of reinforcing fillers. Rubber process oil main purpose is to improve dispersibility of fillers and reduce the viscosity of the rubber compound, therefore enable better processing. Mineral oils are mostly used process oils in natural rubber compounding, but, due to their toxicity and new requirements for preservation of the environment, more and more well-known manufacturers have turned to the use of environmentally friendly process oils. In this study, influence of the hempseed oil as process oil on the products properties in natural rubber compounding was investigated. Properties of hempseed oil as process oil were experimentally determined or calculated. Blending of natural rubber was performed in a laboratory by internal batch mixer, at the constant temperature of 90°C and a rotor speed of 60 rpm. Main rubber properties such as hardness, tensile strength, elongation at break, modulus at 100 and 300% elongation, and rheological properties were determined. Also, voltage and amperage were experimentally measured for calculating power consumption during effective mixing phase in rubber blending.
{"title":"INVESTIGATION OF HEMPSEED PROCESS OIL AS THE ALTERNATIVE IN NATURAL RUBBER COMPOUNDING PROCESS","authors":"Julijana Blagojević, Olga M. Govedarica, Kojić Predrag, O. Bera, M. Jovičić, Sonja Stojanov, J. Pavličević, Dragan D. Govedarica","doi":"10.46793/iccbi21.121b","DOIUrl":"https://doi.org/10.46793/iccbi21.121b","url":null,"abstract":"Good selection of natural rubber compounds is substantial in rubber industry. Behavior of products based on natural rubber is determined by rubber blending components, especially nature of process oil and concentration of reinforcing fillers. Rubber process oil main purpose is to improve dispersibility of fillers and reduce the viscosity of the rubber compound, therefore enable better processing. Mineral oils are mostly used process oils in natural rubber compounding, but, due to their toxicity and new requirements for preservation of the environment, more and more well-known manufacturers have turned to the use of environmentally friendly process oils. In this study, influence of the hempseed oil as process oil on the products properties in natural rubber compounding was investigated. Properties of hempseed oil as process oil were experimentally determined or calculated. Blending of natural rubber was performed in a laboratory by internal batch mixer, at the constant temperature of 90°C and a rotor speed of 60 rpm. Main rubber properties such as hardness, tensile strength, elongation at break, modulus at 100 and 300% elongation, and rheological properties were determined. Also, voltage and amperage were experimentally measured for calculating power consumption during effective mixing phase in rubber blending.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90844103","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}
Andjela A. Franich, Milica N Dimitrijević Stojanović, S. Rajković, M. Jovanovic, M. Jurišević, N. Gajović, N. Arsenijević, I. Jovanovic, Marija D. Živković
Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is anion of malonic (mal, Pt1), 2-methylmalonic (Me-mal, Pt2), 2,2-dimethylmalonic (Me2-mal, Pt3) or 1,1- cyclobutanedicarboxylic (CBDCA, Pt4) acid while 5,6-epoxy-1,10-phen is bidentately coordinated 5,6-epoxy-5,6-dihydro-1,10-phenanthroline were synthesized and characterized by elemental microanalysis, IR, UV-Vis and NMR (1H and 13C) spectroscopic techniques. In vitro anticancer activity of novel platinum(II) complexes have been investigated on human and murine cancer cell lines, as well as normal murine cell line by MTT assay. The obtained results indicate that studied platinum(II) complexes exhibited strong cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. Complex Pt3 display stronger selectivity toward carcinoma cells in comparison to other tested platinum(II) complexes exhibiting beneficial antitumor activity mainly via the induction of apoptosis, as well as inhibition of cell proliferation and migration. Further study showed that Pt3 complex also carry significant in vivo antitumor activity in orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All results imply that these novel platinum(II) complexes have a good anti-tumor effect on breast and colorectal cancer in vivo and in vitro and the affinity to become possible candidates for treatment in anticancer therapy.
{"title":"„IN VITRO“ AND „IN VIVO“ ANTITUMOR ACTIVITY OF PLATINUM(II) COMPLEXES WITH MALONIC ACID ON BREAST AND COLORECTAL CARCINOMA CELL LINES","authors":"Andjela A. Franich, Milica N Dimitrijević Stojanović, S. Rajković, M. Jovanovic, M. Jurišević, N. Gajović, N. Arsenijević, I. Jovanovic, Marija D. Živković","doi":"10.46793/iccbi21.293f","DOIUrl":"https://doi.org/10.46793/iccbi21.293f","url":null,"abstract":"Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is anion of malonic (mal, Pt1), 2-methylmalonic (Me-mal, Pt2), 2,2-dimethylmalonic (Me2-mal, Pt3) or 1,1- cyclobutanedicarboxylic (CBDCA, Pt4) acid while 5,6-epoxy-1,10-phen is bidentately coordinated 5,6-epoxy-5,6-dihydro-1,10-phenanthroline were synthesized and characterized by elemental microanalysis, IR, UV-Vis and NMR (1H and 13C) spectroscopic techniques. In vitro anticancer activity of novel platinum(II) complexes have been investigated on human and murine cancer cell lines, as well as normal murine cell line by MTT assay. The obtained results indicate that studied platinum(II) complexes exhibited strong cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. Complex Pt3 display stronger selectivity toward carcinoma cells in comparison to other tested platinum(II) complexes exhibiting beneficial antitumor activity mainly via the induction of apoptosis, as well as inhibition of cell proliferation and migration. Further study showed that Pt3 complex also carry significant in vivo antitumor activity in orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All results imply that these novel platinum(II) complexes have a good anti-tumor effect on breast and colorectal cancer in vivo and in vitro and the affinity to become possible candidates for treatment in anticancer therapy.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89419207","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. Todorović, G. Stojadinović, Kamal AlJamal, M. Živić
Unlike the neurons in the CNS, the peripheral neurons have certain intrinsic regenerative capacity. After injury, peripheral neurons can switch to a cellular “state for growth”, with the expression profiles similar to early developmental stages. We looked at the changes of morphometric parameters induced in young peripheral neurons with treatments that in adult neurons have growth-stimulatory effect. The experimental treatments compared to control were: BpV (phen), an inhibitor of PTEN; and bFGF, basic fibroblast growth factor. The neurite growth was measured on cultured dissociated dorsal root ganglia neonatal neurons fixed 24h after treatment and immunostained with anti-neurofilament H (NF-H) phosphorylated antibody. FIJI Simple Neurite Tracer was used for morphometry of individual neurons. 24h post treatment, compared to control, total neurite length, length of primary and length of terminal branches, were increased by bFGF but not by BpV treatment. In all measured parameters related to the degree of branching, BpV- treated neurons had small dispersion of values and small mean values, reminiscent of literature data stating that BpV treated neurons are elongated and less branched. However, the BpV did not have a positive influence on neurite elongation, as was reported on adult neurons. In contrast, bFGF stimulated elongation of young neurons in the manner similar to the effects described on the adult neurons.
{"title":"THE MORPHOMETRIC STUDY OF THE EFFECTS OF BISPEROXOVANADIUM (BPV(PHEN)) ON NEONATAL DRG NEURONS IN CULTURE","authors":"N. Todorović, G. Stojadinović, Kamal AlJamal, M. Živić","doi":"10.46793/iccbi21.214t","DOIUrl":"https://doi.org/10.46793/iccbi21.214t","url":null,"abstract":"Unlike the neurons in the CNS, the peripheral neurons have certain intrinsic regenerative capacity. After injury, peripheral neurons can switch to a cellular “state for growth”, with the expression profiles similar to early developmental stages. We looked at the changes of morphometric parameters induced in young peripheral neurons with treatments that in adult neurons have growth-stimulatory effect. The experimental treatments compared to control were: BpV (phen), an inhibitor of PTEN; and bFGF, basic fibroblast growth factor. The neurite growth was measured on cultured dissociated dorsal root ganglia neonatal neurons fixed 24h after treatment and immunostained with anti-neurofilament H (NF-H) phosphorylated antibody. FIJI Simple Neurite Tracer was used for morphometry of individual neurons. 24h post treatment, compared to control, total neurite length, length of primary and length of terminal branches, were increased by bFGF but not by BpV treatment. In all measured parameters related to the degree of branching, BpV- treated neurons had small dispersion of values and small mean values, reminiscent of literature data stating that BpV treated neurons are elongated and less branched. However, the BpV did not have a positive influence on neurite elongation, as was reported on adult neurons. In contrast, bFGF stimulated elongation of young neurons in the manner similar to the effects described on the adult neurons.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75771116","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}
Yaraslau U Dzichenka, M. Shapira, S. Usanov, Marina P. Savić, Ljubica M Grbović, Jovana J. Ajduković, S. Jovanović-Šanta
Our in vitro studies showed that a couple of perspective steroidal derivatives showed previously biomedical potential via enzyme inhibition, receptor binding or antiproliferative effect against the cancer cells of reproductive tissues are able to bind to human CYP7 enzymes – key enzymes taking part in hydroxylation of cholesterol, 25-, 27-hydroxycholesterol and a number of steroidal hormones. In silico screening of binding affinity of the modified steroids toward CYP7 enzymes showed that interaction energy for the new ligands is comparable with consequent values, calculated for the ‘essential’ substrates of the enzymes – cholestenone (CYP7A1) and DHEA (CYP7B1). However, no correlation between binding energy and the affinity of the ligand was found. Novel ligands interact with conserved amino acids taking part in stabilization of natural substrates of CYP7 enzymes. A couple of structural features, governing ligand binding, were identified. Among which are planar structure of A-ring for CYP7A1 ligands, absence of many polar fragments in side-chain and presence of polar group at C3 position. Analysis of the docking results showed that CYP7B1 higher selectivity in comparison with CYP7A1 is connected by the structure of the cavity formed by α-helices I and B`. The data obtained will be used for the explanation of ligand specificity of human sterol- hydroxylases.
{"title":"NOVEL LIGANDS OF HUMAN CYP7 ENZYMES – POSSIBLE MODULATORS OF CHOLESTEROL BLOOD LEVEL: COMPUTER SIMULATION STUDIES","authors":"Yaraslau U Dzichenka, M. Shapira, S. Usanov, Marina P. Savić, Ljubica M Grbović, Jovana J. Ajduković, S. Jovanović-Šanta","doi":"10.46793/iccbi21.435d","DOIUrl":"https://doi.org/10.46793/iccbi21.435d","url":null,"abstract":"Our in vitro studies showed that a couple of perspective steroidal derivatives showed previously biomedical potential via enzyme inhibition, receptor binding or antiproliferative effect against the cancer cells of reproductive tissues are able to bind to human CYP7 enzymes – key enzymes taking part in hydroxylation of cholesterol, 25-, 27-hydroxycholesterol and a number of steroidal hormones. In silico screening of binding affinity of the modified steroids toward CYP7 enzymes showed that interaction energy for the new ligands is comparable with consequent values, calculated for the ‘essential’ substrates of the enzymes – cholestenone (CYP7A1) and DHEA (CYP7B1). However, no correlation between binding energy and the affinity of the ligand was found. Novel ligands interact with conserved amino acids taking part in stabilization of natural substrates of CYP7 enzymes. A couple of structural features, governing ligand binding, were identified. Among which are planar structure of A-ring for CYP7A1 ligands, absence of many polar fragments in side-chain and presence of polar group at C3 position. Analysis of the docking results showed that CYP7B1 higher selectivity in comparison with CYP7A1 is connected by the structure of the cavity formed by α-helices I and B`. The data obtained will be used for the explanation of ligand specificity of human sterol- hydroxylases.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"336 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73142618","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}
Emina Mrkalić, Marina Ćendić Serafinović, Ratomir M. Jelić, Stefana Stojanović, Miroslav Sovrlić
Serum albumin is the major soluble protein in the circulatory system of humans. The metabolism of drugs, their distribution, free concentration, and efficacy depend on the drug-serum albumin interaction [1]. Accordingly, it is important to study the interactions of drugs with serum albumin, which determines the pharmacology and pharmacodynamics of drugs. Quercetin (QUE), a natural polyphenol widely distributed in many plant foods, such as fruits, vegetables, nuts, seeds, grains, and tea [2], bind to serum albumin [3]. Tigecycline (TGC), is a tetracycline antibiotic widely used in the treatment of bacterial infections [4]. This study aimed to investigate the binding properties of TGC to HSA in the presence of QUE, under physiological conditions, by fluorescence spectroscopy.
{"title":"INFLUENCE OF QUERCETIN ON THE BINDING OF TIGECYCLINE TO HUMAN SERUM ALBUMIN","authors":"Emina Mrkalić, Marina Ćendić Serafinović, Ratomir M. Jelić, Stefana Stojanović, Miroslav Sovrlić","doi":"10.46793/iccbi21.363m","DOIUrl":"https://doi.org/10.46793/iccbi21.363m","url":null,"abstract":"Serum albumin is the major soluble protein in the circulatory system of humans. The metabolism of drugs, their distribution, free concentration, and efficacy depend on the drug-serum albumin interaction [1]. Accordingly, it is important to study the interactions of drugs with serum albumin, which determines the pharmacology and pharmacodynamics of drugs. Quercetin (QUE), a natural polyphenol widely distributed in many plant foods, such as fruits, vegetables, nuts, seeds, grains, and tea [2], bind to serum albumin [3]. Tigecycline (TGC), is a tetracycline antibiotic widely used in the treatment of bacterial infections [4]. This study aimed to investigate the binding properties of TGC to HSA in the presence of QUE, under physiological conditions, by fluorescence spectroscopy.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84200443","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}
D. Andrić, Slađana Dukić-Stefanovic, J. Penjišević, I. Jevtić, V. Šukalović, Relja Suručić, Slađana V. Kostić-Rajačić
5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations, revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c) with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM, respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological results are therefore in accordance with the molecular docking simulations thus proving the rational design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new, potential antidepressants.
{"title":"DESIGN, SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF NOVEL N- {4-[2-(4-ARYL-PIPERAZIN-1-YL)-ETHYL]-PHENYL}-ARYLAMIDES","authors":"D. Andrić, Slađana Dukić-Stefanovic, J. Penjišević, I. Jevtić, V. Šukalović, Relja Suručić, Slađana V. Kostić-Rajačić","doi":"10.46793/iccbi21.355a","DOIUrl":"https://doi.org/10.46793/iccbi21.355a","url":null,"abstract":"5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations, revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c) with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM, respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological results are therefore in accordance with the molecular docking simulations thus proving the rational design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new, potential antidepressants.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81736145","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. Jovanović-Šanta, Aleksandar M. Oklješa, A. B. Sachanka, Yaraslau U Dzichenka, S. Usanov
In animal and human organisms, there are many enzymes, members of the family of heme- containing proteins, cytochromes P450 (CYPs), included in the biosynthesis and metabolism of many biomolecules, as cholesterol, bile acids, sex, and corticosteroid hormones, as well as in metabolism of drugs and xenobiotics. It is also well-known that different imidazole and triazole derivatives are efficient inhibitors of CYPs activity. In this study, we present in vitro screening of binding of novel androstane derivatives with tetrazole- containing substituents in position 17 to human recombinant steroid-converting CYP enzymes: CYP7A1, CYP7B1, CYP17A1, CYP19, and CYP21. Initial screening was performed using a high throughput screening approach, while the affinity of the ligands was analyzed using spectrophotometric titration. For some among tested compounds type I spectral response (substrate-like binding) for CYP7A1 selectively, while for one compound type II spectral response (inhibitor-like binding) for CYP21 were detected, with micromolar values of Kds. Interestingly, one compound with mixed spectral response was found to bind for CYP7B1, which means that there are two optimal positions of the ligand inside the protein active site. Such results could be useful in CYP-inhibiting drug development, during a fast, high-throughput screening of pharmacological potential of novel compounds, as well as in side- effects recognizing.
{"title":"17-SUBSTITUTED STEROIDAL TETRAZOLES – NOVEL LIGANDS FOR HUMAN STEROID-CONVERTING CYP ENZYMES","authors":"S. Jovanović-Šanta, Aleksandar M. Oklješa, A. B. Sachanka, Yaraslau U Dzichenka, S. Usanov","doi":"10.46793/iccbi21.336js","DOIUrl":"https://doi.org/10.46793/iccbi21.336js","url":null,"abstract":"In animal and human organisms, there are many enzymes, members of the family of heme- containing proteins, cytochromes P450 (CYPs), included in the biosynthesis and metabolism of many biomolecules, as cholesterol, bile acids, sex, and corticosteroid hormones, as well as in metabolism of drugs and xenobiotics. It is also well-known that different imidazole and triazole derivatives are efficient inhibitors of CYPs activity. In this study, we present in vitro screening of binding of novel androstane derivatives with tetrazole- containing substituents in position 17 to human recombinant steroid-converting CYP enzymes: CYP7A1, CYP7B1, CYP17A1, CYP19, and CYP21. Initial screening was performed using a high throughput screening approach, while the affinity of the ligands was analyzed using spectrophotometric titration. For some among tested compounds type I spectral response (substrate-like binding) for CYP7A1 selectively, while for one compound type II spectral response (inhibitor-like binding) for CYP21 were detected, with micromolar values of Kds. Interestingly, one compound with mixed spectral response was found to bind for CYP7B1, which means that there are two optimal positions of the ligand inside the protein active site. Such results could be useful in CYP-inhibiting drug development, during a fast, high-throughput screening of pharmacological potential of novel compounds, as well as in side- effects recognizing.","PeriodicalId":9171,"journal":{"name":"Book of Proceedings: 1st International Conference on Chemo and BioInformatics,","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87887764","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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