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Vol.5 , No. 1, Publication Date: Apr. 19, 2019, Page: 1-13
, Molecular Docking and Photo–Induced Cleavage&description=(2<i>E</i>)-3-(furan-2-yl)-1-(pyridin-4-yl)prop-2-en-1-one1 reacted with 2-cyanoethane-thioamide (2) to afford the corresponding 6'–(2–thienyl)–2'–thioxo–1',2'–dihydro–3,4'–bipyridine–3'–carbonitrile 4. The synthetic potentiality of 4 was investigated through electrophilic substitution reactions using several electrophilic C–species to afford Ethyl {[3'–cyano–6'–(2–thienyl)–3,4'–bipyridin–2'–yl]thio}acetate 5 in very pure state and in a good yield. 3–amino–4–pyridin–3–yl–6–(2–thienyl)thieno[2,3–<i>b</i>]pyridine–2–carbohydrazides (7) was synthesized in good and pure yield <i>via</i> the reaction of ethyl {[3'–cyano–6'–(2–thienyl)–3,4'–bipyridin–2'–yl]thio}acetate (5) with hydrazine hydrate. The structures of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, <sup>1</sup>H NMR, mass spectra as well as that of elemental analyses. In the biological applications, the interaction of compound 7 with human serum albumin (HSA) was investigated under physiological condition in Tris–HCl buffer solution at pH 7.4 by means of various spectroscopic methods (fluorescence, CD and FTIR) and molecular docking technique. The results of fluorescence titration revealed that the compound 7 strongly quench the intrinsic fluorescence of HSA through a static quenching procedure. Binding constants (<i>K<sub>b</sub></i>) and the number of binding sites (n≈1) were calculated using modified Stern–Volmer equations. The thermodynamic parameters <i>∆G</i> at different temperatures were calculated subsequently the value of <i>∆H</i> and <i>∆S</i> was also calculated which revealed that the hydrophobic and hydrogen bonding interactions play a major role in HSA–compound 7 association. The molecular docking technique was utilized to ascertain the mechanism and mode of action towards the molecular target HSA indicating that compound 7 was located within the subdomain IIA of protein by electrostatic interactions and hydrogen bonds, consistent with the corresponding experimental results. Additionally, compound 7 shows efficient photo-induced HSA cleavage. The results may provide valuable information to understand the mechanistic pathway of drug delivery and to pharmacological behavior of drug.&picture=http://www.aascit.org/aascit/decorators/img/journal/978.jpg)
| [1] | Ahmed Ali Al-Hazmi, Department of Chemistry, Ibb University, Ibb, Yemen. |
| [2] | Waddhaah M. Al–asbahy, Department of Chemistry, Ibb University, Ibb, Yemen. |
| [3] | Faisel Aqlan, Department of Chemistry, Ibb University, Ibb, Yemen. |
| [4] | Sabah Ahmed Abdo Esmail, Department of Chemistry, Ibb University, Ibb, Yemen. |
| [5] | Manal Shamsi, Department of Chemistry, Ibb University, Ibb, Yemen. |
| [6] | Sahar Mansour Al–Sabahi, Department of Chemistry, Ibb University, Ibb, Yemen. |
| [7] | Labeeb M. Shaif, Department of Chemistry, Ibb University, Ibb, Yemen. |
(2E)-3-(furan-2-yl)-1-(pyridin-4-yl)prop-2-en-1-one1 reacted with 2-cyanoethane-thioamide (2) to afford the corresponding 6'–(2–thienyl)–2'–thioxo–1',2'–dihydro–3,4'–bipyridine–3'–carbonitrile 4. The synthetic potentiality of 4 was investigated through electrophilic substitution reactions using several electrophilic C–species to afford Ethyl {[3'–cyano–6'–(2–thienyl)–3,4'–bipyridin–2'–yl]thio}acetate 5 in very pure state and in a good yield. 3–amino–4–pyridin–3–yl–6–(2–thienyl)thieno[2,3–b]pyridine–2–carbohydrazides (7) was synthesized in good and pure yield via the reaction of ethyl {[3'–cyano–6'–(2–thienyl)–3,4'–bipyridin–2'–yl]thio}acetate (5) with hydrazine hydrate. The structures of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses. In the biological applications, the interaction of compound 7 with human serum albumin (HSA) was investigated under physiological condition in Tris–HCl buffer solution at pH 7.4 by means of various spectroscopic methods (fluorescence, CD and FTIR) and molecular docking technique. The results of fluorescence titration revealed that the compound 7 strongly quench the intrinsic fluorescence of HSA through a static quenching procedure. Binding constants (Kb) and the number of binding sites (n≈1) were calculated using modified Stern–Volmer equations. The thermodynamic parameters ∆G at different temperatures were calculated subsequently the value of ∆H and ∆S was also calculated which revealed that the hydrophobic and hydrogen bonding interactions play a major role in HSA–compound 7 association. The molecular docking technique was utilized to ascertain the mechanism and mode of action towards the molecular target HSA indicating that compound 7 was located within the subdomain IIA of protein by electrostatic interactions and hydrogen bonds, consistent with the corresponding experimental results. Additionally, compound 7 shows efficient photo-induced HSA cleavage. The results may provide valuable information to understand the mechanistic pathway of drug delivery and to pharmacological behavior of drug.
Keywords
Human Serum Albumin (HSA), Fluorescence Quenching, Molecular Modeling, Carbohydrizide Drugs, Photo–Induced Cleavage
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