QSAR-ANALYSIS OF POLYSUBSTITUTED FUNCTIONALIZED AMINOTHIAZOLES WITH ANTIHYPERTENSIVE ACTIVITY
DOI:
https://doi.org/10.11603/ijmmr.2413-6077.2019.2.10898Keywords:
polysubstituted functionalized aminothiazoles, antihypertensive activity, molecular descriptors, QSAR-analysisAbstract
Background. QSAR analysis is an important tool for the identification of pharmacophore fragments in biologically active substances and helps optimize the search for new effective drugs.
Objective. The aim of the study was to determine the molecular descriptors for QSAR analysis of polysubstituted functionalized aminothiazoles as a theoretical basis for purposeful search de novo of potential antihypertensive drugs among the investigated compounds.
Methods. Calculation of molecular descriptors and QSAR-models creation was carried out using the Hyper-Chem 7.5 and BuildQSAR packages.
Results. The calculation of a number of molecular descriptors (electronic, steric, geometric, energy) was performed for 15 new polysubstituted functionalized aminothiazoles, with established in vivo antihypertensive activity. According to the calculated molecular descriptors and antihypertensive activity parameter, the QSAR models were derived НА = a + b ∙ X1 + c ∙ X2 + d ∙ X3 , where the activity parameter НА is antihypertensive activity and X1, X2, X3 are molecular descriptors.
Conclusion. The study of ‘the structure - antihypertensive activity’ relationship for polysubstituted functionalized aminothiazoles was carried out. QSAR analysis revealed that volume, area, lipophilicity, dipole moment, refractivity, polarization of the molecule and energy of the lowest unoccupied molecular orbital have the most significant effect on antihypertensive activity. It was suggested that the attained QSAR-models may have antihypertensive activity within abovementioned row of compounds and can be considered as theoretical basis for de novo design of new potential antihypertensive drugs.
References
Cherkasov A, Muratov EN, Fourches D, Varnek A, Baskin II, Cronin M, Dearden J, Gramatica P, Martin YC, Todeschini R, Consonni V. QSAR modeling: where have you been? Where are you going to?. Journal of Medicinal Chemistry. 2014 Jan 6;57(12): 4977-5010.
doi:10.1021/jm4004285 DOI: https://doi.org/10.1021/jm4004285
Wang T, Wu MB, Lin JP, Yang LR. Quantitative structure – activity relationship: promising advances in drug discovery platforms. Expert Opinion on drug Discovery. 2015 Dec 2;10(12):1283-300.
doi: 10.1517/17460441.2015.1083006 DOI: https://doi.org/10.1517/17460441.2015.1083006
Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, Makarenko AS, Tanchuk VY. Virtual computational chemistry laboratory–design and description. Journal of Computer-Aided Molecular Design. 2005 Jun 1;19(6):453-63.
doi: 10.1007/s10822-005-8694-y DOI: https://doi.org/10.1007/s10822-005-8694-y
Giri RS, Thaker HM, Giordano T, Williams J, Rogers D, Sudersanam V, Vasu KK. Design, synthesis and characterization of novel 2-(2, 4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents. European journal of medicinal chemistry. 2009 May 1;44(5):2184-9.
doi: 10.1016/j.ejmech.2008.10.031 DOI: https://doi.org/10.1016/j.ejmech.2008.10.031
Abdel-Wahab BF, Mohamed SF, Amr AE, Abdalla MM. Synthesis and reactions of thiosemicarbazides, triazoles, and Schiff bases as antihypertensive α-blocking agents. Monatshefte für Chemie-Chemical Monthly. 2008 Sep 1;139(9):1083-90.
doi: 10.1007/s00706-008-0896-2 DOI: https://doi.org/10.1007/s00706-008-0896-2
Drapak I, Perekhoda L, Demchenko N, Suleiman M, Rakhimova M, Demchuk I, Taran S, Seredynska N, Gerashchenko I. Cardioprotective Activity of Some 2-Arylimino-1, 3-Thiazole Derivatives. Scientia Pharmaceutica. 2019 Mar;87(1):7-8.
doi: 10.3390/scipharm87010007 DOI: https://doi.org/10.3390/scipharm87010007
Perekhoda L, Yeromina H, Drapak I, Kobzar N, Smolskiy O, Demchenko N. The antioxidant properties of 1-[2-(R-phenylimino)-4-methyl-3-(3-[morpholine-4-yl] propyl)-2, 3-dihydro-1, 3-thiazol-5-yl] ethane-1-one derivatives under conditions of artificial oxidative stress in vitro. Saudi Journal of Medical and Pharmaceutical Sciences. 2017;3(1):55-9.
doi: 10.21276/sjmps.2017.3.9
Yeromina HO, Drapak IV, Perekhoda LO, Yaremenko VD, Demchenko AM, Perekhoda LA. Synthesis of 2-(4-aryl (adamantyl)-2-phenylіmіnothіazol-3-yl)-ethanol derivatives and prediction of their biological activity. Der Pharma Chemica. 2016;8(3):64-70.
Drapak IV, Zimenkovsky BS, Seredynska NM, Demchenko AM. 1-{3-[2-(3,4-Dimethoxy-phenyl)- ethyl]-4-methyl-1-2-phenylimino-2,3-dihydro-thiazol-5-yl}-ethanone hydrochloride, which is antihypertensive action. No 19960 UA Patent UA. 2019 August 27.
Laxmi K. Structural Elucidation of Drug Aspirin by Using Various Software Tools Like HyperChem, Argus Lab, ChemSketch, Avogrado and Chemeo Database. J Theor Comput Sci. 2019;5(163):2.
De Oliveira DB, Gaudio AC. BuildQSAR: a new computer program for QSAR analysis. Quantitative Structure-Activity Relationships: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis. 2000 Dec;19(6):599-601. DOI: https://doi.org/10.1002/1521-3838(200012)19:6<599::AID-QSAR599>3.0.CO;2-B
doi: 10.1002/1521-3838(200012)19:6%3C599:: AID-QSAR599%3E3.0.CO;2-B
Todeschini R, Consonni V. Handbook of Molecular Descriptors. 2000. NY, Toronto: Wiley-VCH.
doi: 10.1002/9783527613106 DOI: https://doi.org/10.1002/9783527613106
Todeschini R, Consonni V. Molecular descriptors for chemoinformatics: volume I: alphabetical listing/volume II: appendices, references. John Wiley & Sons; 2009 Oct 30.
doi: 10.1002/9783527628766 DOI: https://doi.org/10.1002/9783527628766
Downloads
Published
How to Cite
Issue
Section
License
Authors who sent their manuscript to International Journal of Medicine and Medical Research agree to the following terms:
1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License CC-BY-NC that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
2. Authors able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
