https://journals.4science.ge/index.php/GS/index 1 Georgian Scientists Vol. 3 Issue 4, 2021 https://doi.org/10.52340/gs.2021.11.01 Synthesis and biological activity of Hepta-O-acetyl-1-O-(2-chloro-3-phenyl thio propyl)- - D-maltose L.V. Tabatadze1, N.N. Sidamonidze2, D.B. Gulbani3, D.J. Iremashvili4 1,3Department of Chemistry, Sokhumi State University, Ana Politkovskaia str. 61, 0186, Tbilisi, Georgia 2Department of Chemistry, Iv. Javakhishvili Tbilisi State University, I.Chavchavadze Ave., 0179 Tbilisi,Georgia 4Laboratory of Analytical Chemistry and Mineral Enrichment, G. Tsulukidze Mining Institute, E. Mindeli, str.7, 0186 Tbilisi, Georgia Corresponding Author E-mail: l.tabatadze@sou.edu.ge ABSTRACT Carbohydrate derivatives are distinguished with wide range of biological activity which is proven by successful usage of preparations made of Carbohydrate based in different branches of pharmaceutical chemistry. As a result of research of Carbohydrate compounde, the relationship between unique structure and its chemical and biological properties has been studied. Input of bulk liphophilic adamantine moiety in the proved medications or biologically active molecule in most cases is improved molecule’s biological characteristic, drug’s lipopilycity and prolonged actin is enhanced, and at the same time toxicity and side negative effects is reduced.We studied the reactions of acetylaryl glycosides with phenylsulfonyl chloride in the presence of a benzoyl peroxide catalyst. A new sulfur-containing glucoside was synthesized: Hepta-O-acetyl-1-O-(2-chloro-3- phenyl thio propyl) -D-maltose. The bactericidal properties of -O-(2-chloro-3-phenyl thio propyl)-D-maltose of the obtained product after deacetylation were studied. With the help of the computer program PASS (Prediction of Activity Spectra for Substance) onlaines were able to predict the range of activity of substances. The obtained result established correlations on bactericidal properties between biological activity and the intended biological activity. The structure of the synthesized compounds was determined by physico-chemical research methods. Keywords: Thioglycosides, maltose, Benzoyl peroxide, Phenylsulfonyl chloride, Biological activity Introduction Analysis of the scientific literature in recent years shows that the interest of chemical researchers in the synthesis of products containing bromides, thio sugars, disaccharides containing 1,2-O-glycoside bond has increased dramatically [1]. Studies in this area are expected to lead to the development of new, less toxic, biologically and physiologically active drugs. Due to the urgency of the topic, it is important to conduct scientific research in this https://journals.4science.ge/index.php/GS/index 2 area. The development of methods for the synthesis of Carbohydrate derivatives is one of the important tasks of bioorganic chemistry and has direct interdisciplinary application in the production of biology, medicine, agricultural biotechnology, food industry, pharmaceuticals. In recent years, the introduction of thio sugars into the structure of physiologically active substances and pesticides to "improve" them, which is one of the most progressive ways to protect a living cell [2-4]. In medical practice, the use of sulfur is based on its ability, when interacting with organic substances of the body, to form sulfides and pentathionic acid, on the presence of which keratolytic, antimicrobial and antiparasitic effects depend. As a result of research of glycoside compounds, the relationship between unique structure and its chemical and biological properties has been studied [5-7]. Important compounds of carbohydrate origin are thioglycosides. Recent studies have shown that these compounds are characterized by very significant biological activity and are included in the composition of vitamins, enzymes and coenzymes. Sulfur-containing compounds are used as an antispasmodic effect, as well as an extension of the capillaries [8-9]. For the synthesis of sulfur-containing maltose, the reaction of the addition of Disaccharides (maltose) with phenylsulfonyl chloride was first studied. The starting compounds are synthesized by known methods [10]. Experimental Part 1-O-allyl-hepta-O-acetyl-maltose was synthesized from an acetylated disaccharide in the presence of a BF3 [(C2H5)2O] catalyst. By dissolving the allylated disaccharide in chloroform at room temperature, in a nitrogen atmosphere with constant stirring, adding dropwise a solution of phenylsulfonyl chloride (dissolved in CCI4), a new compound was synthesized: Hepta-O-acetyl-1-O- (2-chloro-3-phenyl thio propyl) -D-maltose with a yield of 56%. The synthesized compounds are white, very soluble in chloroform. The composition of the derivative was determined by physico-chemical research methods [11]. Composition of compounds, physical and chemical characteristics will be determined by instrumental research methods (elemental, polarimetric, chromatographic analyzes, the so-called BMR 13C and BMR 1H spectroscopy. The definition of optical rotation using elemental analysis, IR and 13C Spectroscopy. The purity of thesubstance as checked using thinlayer chromatography using ''silufol'' plate in the following solvent system by volume: chloroform-ethanol 1:1. Optical rotation was measured on a SU-3 universal saccharimeter at 20 0C. IR spectra of the samples were taken on a UR-20 spectrometer in KBr tablets. 13C NMR was recorded on a Bruker AM- 300,75.5 MHz spectrometer in deuterochloroforme: https://journals.4science.ge/index.php/GS/index 3 Characteristics Hepta-O-acetyl-1-O-(2-chloro-3-phenyl thio propyl)- -D-maltose (3) tab. 1 Compound Brutal-formule Melting point t 0C Rf Molecular mass ]tD CHCI3 Outcome G % 3 C35H45018SCI 92-96 0.63 820.5 -150(t=200) 0.68 56 13C NMR Spectroscopic analysis Compound 3 tab. 2 168,7-175,8 7RO-CO-CH3 20,6-20,7 7RO-CO-CH3’ 60.980 R-O-CH2 100.8; 92.0 C-1; C-1' 61.8; 61.4 C-6; C-6' 77.5; 76.65; 71.05; 70.8; 67.8; 66.8 C2-6; C2-5' 29.725-19.386 -CH2 127.1-137.086 C6H5 IR Spectroscopic analysis Compound 3 tab. 3 C-O-C C-S C-CI C-Harom CH2 CH3 1061.1147 453.600 690.739 3070 2924 2850 https://journals.4science.ge/index.php/GS/index 4 This substance has a wide range of predicted biological activities. Prediction of the biological activity of the synthesized carbohydrate product: Hepta-O-acetyl-1-O-(2-chloro-3-phenyl thio propyl) -D-maltose and free hydroxyl-containing hepta-O-1-O-(2-chloro-3-phenyl thio propyl) -D-maltose was performed using the PASS (Prediction of Activity Spectra for Substance) ONLAINE computer program [12]. The specified computer program evaluated the biological activity of Hepta-O-acetyl-1-O-(2-chloro-3-phenyl thio propyl)- -D-maltose (3) (tab. 4) and his deacetylated product Hepta-O-1-O-(2-chloro-3-Phenylthiopropyl) - D-maltose (4) (tab. 5). Biological activity of Hepta-O-acetyl-1-O- (2-chloro-3-phenyl thio propyl)- -D-maltose (3) O OAc H H H OAc H AcO OCH2 CH CH2 S C6H5Cl O AcO H OAc H H OAc H AcO O tab.4 All Pa*>Pi** Pa>0,3 Pa>0,7 0,858 0,010 Benzoate-CoA ligase inhibitor 0,810 0,010 Antineoplastic 0,709 0,005 Antileukemic 0,692 0,009 Cholesterol antagonist 0,627 0,007 Antibacterial 0,587 0,004 Antineoplastic (cervical cancer) 0,596 0,030 Immunosuppressant 0,568 0,022 Antifungal 0,543 0,008 Angiogenesis stimulant 0,525 0,033 Hypolipemic 0,451 0,009 Protein synthesis inhibitor 0,542 0,122 Membrane permeability inhibitor 0,389 0,006 Antimycoplasmal 0,318 0,047 DNA synthesis inhibitor 0,296 0,080 Immunostimulant 0,248 0,037 Antioxidant 0,254 0,068 Antiprotozoal https://journals.4science.ge/index.php/GS/index 5 0,245 0,097 Cytostatic 0,220 0,093 Lactose synthase inhibitor 0,242 0,115 Antimetastatic 0,248 0,131 Antiviral (Herpes) 0,168 0,051 Sucrose-phosphate synthase inhibitor 0,255 0,139 Antithrombotic 0,220 0,119 Macrophage stimulant 0,104 0,010 1,3-Beta-glucan synthase inhibitor 0,143 0,060 Antihemorrhagic 0,137 0,103 Alpha-amylase inhibitor 0,041 0,010 Beta glucosidase inhibitor 0,255 0,227 Sugar-phosphatase inhibitor 0,167 0,140 Antiviral (Hepatitis B) 0,181 0,161 Antitoxic 0,146 0,132 Antiparasitic 0,200 0,197 Antiprotozoal (Leishmania) 0,046 0,046 Beta galactosidase inhibitor Biological activity of deacetylated product Hepta-O-1-O- (2-chloro-3-Phenylthiopropyl) -D-maltose (4) O OH H H H OH H HO OCH2 CH CH2 S C6H5Cl O HO H OH H H OH H HO O https://journals.4science.ge/index.php/GS/index 6 tab.5. All Pa*>Pi** Pa>0,3 Pa>0,7 0,934 0,003 Benzoate-CoA ligase inhibitor 0,859 0,004 Cholesterol antagonist 0,791 0,018 Sugar-phosphatase inhibitor 0,737 0,005 Lactase inhibitor 0,722 0,022 Antineoplastic 0,689 0,004 Angiogenesis stimulant 0,644 0,007 Antileukemic 0,597 0,009 Antibacterial 0,592 0,004 Antineoplastic (cervical cancer) 0,581 0,018 Antithrombotic 0,559 0,028 Immunostimulant 0,549 0,019 Cytostatic 0,542 0,021 Radioprotector 0,531 0,026 Antifungal 0,520 0,016 Antimetastatic 0,501 0,005 Alpha-amylase inhibitor 0,497 0,006 Lactose synthase inhibitor 0,490 0,024 Bilirubin oxidase inhibitor 0,489 0,045 Immunosuppressant 0,449 0,017 Protein-tyrosine sulfotransferase inhibitor 0,472 0,042 Hypolipemic 0,429 0,011 Protein synthesis inhibitor A comparison of the PASS predictions data showed, that similar biological activities: Cholesterol antagonist, Angiogenesis stimulant, Immunostimulant, Cytostatic, Lactose synthase inhibitor, Antimetastatic, Antithrombotic, Sugar-phosphatase inhibitor, Protein synthesis inhibitor - compound-4 has with higher Pa value than substance-3 and biological activity: Antifungal, Antineoplastic, Antibacterial is relatively low Pa. And, substance-3 has Antitoxic, Antiprotozoal (Leishmania), Beta galactosidase inhibitor, Beta glucosidase inhibitor, Antihemorrhagic, Membrane permeability inhibitor, Antimycoplasmal, DNA synthesis inhibitor, properties that substance 4 does not. Based on a generalization of a vast literary material, biologically active compounds are characterized by a certain specificity of composition and structure. Structural modification of compounds by introducing various molecules or atomic groups in a molecule can determine the effect of molecular separation of fragments on bioactivity. Pa (probability "to be active") estimates the chance that the studied compound is belonging to the sub-class of active compounds. Pi (probability "to be inactive") estimates the chance that the studied compound is belonging to the sub-class of inactive compounds. https://journals.4science.ge/index.php/GS/index 7 Conclusion From a theoretical and practical point of view, is especially interesting to establish some correlation between structure and biological activity, which serves to search for the biological properties of new compounds with preliminary predictions. By assessment of structure-activity relationships biological activity spectrum of synthesized glycosides have been revealed. The results of the study will enable us providing selection of the most prospective compounds from the set of synthesized samples. References 1. Robert J. Ferrier; Radical-Mediated Brominations at Ring Positions of Carbohydrates January, Advances in Carbohydrate Chemistry and Biochemistry 2010, 49(3):37-92. 2. Anna Czubatka-Bienkowska, Anna Macieja, Joanna Sarnik, Zbigniew J. 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Orianne Cholet, Alain He´naut, Serge Casaregola, and Pascal Bonnarme; Gene Expression and Biochemical Analysis of Cheese-Ripening Yeasts: Focus on Catabolism of L-Methionine, Lactate, and Lactose; American Society for Microbiology. 2007, 73, 8. pp. 2561-2570 https://journals.4science.ge/index.php/GS/index 8 10. John A Sturman, Yong Y Lin, Tetsuo Higuchi & J H Fellman; N-Acetylneuramin Lactose Sulfate: A Newly Identified Nutrient in Milk. 1985, 19, pp. 216-219. 11. N.N. Sidamonidze, R.O. Vardiashvili, K.Z. Onashvili, L.V. Tabatadze; Synthesis and Bactericidal Properties Sulfur-Containing 1,2-Trans-Glycosides; Black Sea Scientific J. Of Academic Research. Eesti, Tallin 2018, 41, 0,3. pp. 35-44. 12. L.V. Tabatadze, N.N. Sidamonidze, R.O. Vardiashvili, K.Z. Onashvili. Synthesis and biological activity of 2,3,4,6-tetra-o-acetyl-1-O-(2-chloro-3-phenyl thio propyl)- -D-Glucopyranose; "Annals of Agrarian Science; 2019, 17(3): 355-361. https://www.elsevier.com/journals/annals-of-agrarian-science -O- -1-O-(2- -3- )- -D- , , , , . . . . . : -O- -1-O-(2- -3- )- -D- . - O-(2- -3- )-D- PASS onlaines - (Prediction of Activity Spectra for Substance) . PASS- . . : , , , ,