Error message

  • Deprecated function: Unparenthesized `a ? b : c ? d : e` is deprecated. Use either `(a ? b : c) ? d : e` or `a ? b : (c ? d : e)` in include_once() (line 1439 of /home/science2016/public_html/includes/bootstrap.inc).
  • Deprecated function: Array and string offset access syntax with curly braces is deprecated in include_once() (line 3557 of /home/science2016/public_html/includes/bootstrap.inc).

Синтез, антимікробні й обчислювальні дослідження нових похідних розгалужених азафенотіазинонів

FideliaN. Ibeanu1, MercyA. Ezeokonkwo2, EfeturiA. Onoabedje2, Cosmas C. Eze1,2,4, Evelyn U. Godwin-Nwakwasi3, UchechukwuC. Okoro2
Affiliation: 
1Natural Science Unit, School of General Studies, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria 2Departmentof Pure and Industrial Chemistry, University of Nigeria, Nsukka, 410001, Enugu State, Nigeria 3Department of Chemistry, Gregory University, Uturu, Abia State, Nigeria 4Department of Chemistry, North Carolina State University, Raleigh, North Carolina, 27607, USA efeturi.onoabedje@unn.edu.ng
DOI: 
https://doi.org/10.23939/chcht17.04.786
AttachmentSize
PDF icon full_text.pdf370.88 KB

Keywords:

Abstract: 
У процесі постійного пошуку нових медикаментозно активних нелінійних фенотіазинів синтезовано нові кутові похідні хлороазафенотіазинону за допомогою реакцій перехресного приєднання, каталізованих перехідними металами. Структурну будову синтезованих сполук встановлено за допомогою комбінованого спектроскопічного й елементного аналізу. Синтезовані сполуки були протестовані на антимікробну активність щодо ізолятів Bacillussubtilis, Staphylococcusaureus, Enterococusfaecalis, Escherichiacoli, Candidaalbican та Aspergillusniger методом конвекційного розведення в агаровому середовищі, і сполуки 5c та 8c виявили відмінну активність invitro проти деяких з досліджуваних мікроорганізмів. Дослідження insilico показало, що синтезовані сполуки мають перспективні фізико-хімічні властивості та добре вписуються в активний центр біотин-протеїнової лігази (BPL), утворюючи необхідні водневі зв'язки та гідрофобні взаємодії.
References: 

[1] Onoabedje, E.A.;Egu, S.A.; Ezeokonkwo M.A.; Okoro, U.C. Highlights of Molecular Structures and Applications of Phenothiazine & Phenoxazine Polycycles.J MolStruct.2019,1175, 956–962.https://doi.org/10.1016/j.molstruc.2018.08.064
[2] Posso, M.C.; Domingues, F.C.; Ferreira, S.; Silvestre, S. Development of phenothiazine hybrids with Potential Medicinal Interest: A Review. Molecules2022, 27, 276. https://doi.org/10.3390/molecules27010276
[3] Pluta, K.;Jeleń, M.;Morak-Młodawska, B.; Zimecki, M.; Artym, J.;Kocięba, M.;Zaczyńska, E. Azaphenothiazines – Promising Phenothiazine Derivatives. An Insight into Nomenclature, Synthesis, Structure Elucidation and Biological Properties. Eur J Med Chem. 2017, 138, 774–806. https://doi.org/10.1016/j.ejmech.2017.07.009
[4] Montoya, M.C.; DiDone, L.; Heier, R.F.; Meyers, M.J.; Krysan, D.J. Antifungal Phenothiazines: Optimization, Characterization of Mechanism, and Modulation of Neuroreceptor Activity. ACS Infect. Dis.2018,4, 499–507. https://doi.org/10.1021/acsinfecdis.7b00157
[5] Wen, B.; Zhou, M. Metabolic Activation of the Phenothiazine Antipsychotic Chlorpromazine and Thioridazineto ElectropholicIminoquinone Species in Human Liver Microsomesand Recombinant P450s. Chem. Biol. Interact.2009,181, 220–226.https://doi.org/10.1016/j.cbi.2009.05.014
[6] Sadanandam, Y.S.; Shetty, M.M.; Rao, A.B.; Rambabu, Y. 10H-Pehnothiazines: A New Class of Enzyme Inhibitors for Inflammatory Diseases. Eur. J. Med. Chem.2009, 44, 197–202.https://doi.org/10.1016/j.ejmech.2008.02.028
[7] Gopi, C.; Dhanaraju, M.D. Recent Progress in Synthesis, Structure and Biological Activities of Phenothiazine Derivatives. Rev. J. Chem.2019, 9,95–126. https://doi.org/10.1134/S2079978019020018
[8] Trivedi, A.R.; Siddiqui, A.B.; Shah, V.H. Design, Synthesis, Characterization and Antitubercular Activity of some 2-Heterocycle Substituted Phenothiazines.Arkivoc2008,2, 210–217.https://doi.org/10.3998/ark.5550190.0009.223
[9] Siddiqui, N.; Alam, S.M.; Ahsan, W. Synthesis, Anticonvulsant and Toxicity Evaluation of 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl)hydrazine. Acta Pharm. 2008, 58, 445–54. https://doi.org/10.2478/v10007-008-0025-0
[10] Kumar, A.; Gurtu, S.; Agarwal, J.C.; Sinha, J.N.; Bhargava K.P.; Shanker, K. Synthesis and Cardiovascular Activity of Substituted 4-Azetidinones. J. Indian Chem. Soc.1983, 60, 608–610. https://doi.org/10.5281/zenodo.6348916
[11] Venkatesan, K.; Satyanarayana, V.S.V.; Sivakumar, A. Synthesis and Biological Evaluation of Novel Phenothiazine Derivatives as Potential Antitumor Agents. PolycyclAromatCompd2023, 43, 850–859. https://doi.org/10.1080/10406638.2021.2021254
[12] Onoabedje, E.A.;Okafor, S.N.; Akpomie, K.G.; Okoro, U.C. The Synthesis and Theoretical Anti-Tumor Studies of Some New Monoaza-10H-Phenothiazine and 10H-Phenoxazine Heterocycles. Chem. Chem. Technol.2019, 13, 288–295. https://doi.org/10.23939/chcht13.03.288
[13] González-González, A.; Vazquez-Jimenez, L.K.; Paz-González, A.D.; Bolognesi, M.L.; Rivera G. Recent Advances in the Medicinal Chemistry of Phenothiazines, New Anticancer and Antiprotozoal Agents. Curr Med Chem.2021, 28, 7910–7936. https://doi.org/10.2174/0929867328666210405120330
[14] Pluta, K.; Jeleń, M.; Morak-Młodawska, B.; Zimecki, M.; Artym, J.; Kocięba, M.; Anticancer Activity of Newly Synthesized Azaphenothiazinesfrom NCI's Anticancer Screening Bank. Pharmacol. Rep. 2010, 62, 319–332.https://doi.org/10.1016/s1734-1140(10)70272-3
[15] Aarestrup, F.M. Occurrence of Glycopeptide Resistance among Enterococcus faecium Isolates from Conventional and Ecological Poultry Farms. Microb. Drug Resist.2009,1, 255–257.https://doi.org/10.1089/mdr.1995.1.255
[16] Threlfall, E.J.; Ward, L.R.; Skinner, J.A.; Rowe, B. Increase in Multiple Antibiotic Resistance in Nontyphoidal Salmonellas from Humans in England and Wales: A Comparison of Data for 1994 and 1996. Microb.Drug Resist.2009,3, 263–266.https://doi.org/10.1089/mdr.1997.3.263
[17] Onoabedje, E.A.; Okoro, U.C.; Knight, D.W. Rapid Access to New Angular Phenothiazine and Phenoxazine Dyes. J. HeterocyclicChem.2017, 54, 206–214.https://doi.org/10.1002/jhet.2569
[18] Onoabedje, E.A.;Okoro, U.C.; Sarkar, A.; Knight, D.W. Synthesis and Structure of New Alkynyl Derivatives of Phenothiazine and Phenoxazine. J. Sulfur Chem. 2016, 34, 269–281. http://dx.doi.org/10.1080/17415993.2015.1131827
[19] Onoabedje, E.A.; Okoro, U.C.; Sarkar, A.; Knight, D.W. Fuctionalization of Linear and Angular Phenothiazine and Phenoxazine Ring Systems viaPd(0)/XPhos Mediated Suzuki-Miyaura Cross-coupling Reactions. J Heterocyclic Chem. 2016,53, 1787–1794. https://doi.org/10.1002/jhet.2485
[20] Ibeanu, F.N.; Onoabedje, E.A.; Ibezim, A.; Okoro,U.C. Synthesis, Characterization, Computational and Biological Study of Novel Azabenzo[a]phenothiazine and Azabenzo[b]phenoxazineHeterocycles as Potential Antibiotic Agent. Med Chem Res. 2018,27, 1093–1102.https://doi.org/10.1007/s0044-017-2131-3
[21] Yu, X-Q.; Yamamoto, Y.; Miyaura, N. Aryl Triolborates: Novel Reagent for copper catalyzed N-Arylation of Amines, Amines, Anilines and Imidazoles.Chem. Asian J.2008, 3, 1517–1522. https://doi.org/10.1002/asia.200800135
[22] Yamamoto, Y.; Takizawa, M.; Yu, X.-Q.; Miyaura, N. Cyclic Triolborates: Air and Water-Stable Ate Complexes of Organoboronic Acids. Angew. Chem. 2008, 120, 942–945. https://doi.org/10.1002/ange.200704162
[23] Yamamoto, Y. Cyclic Triolborate Salts: Novel Reagent for Organic Synthesis. Heterocycles2012,85, 799–819.https://doi.org/10.3987/REV-12-728
[24] Reller, L.B.; Weinstein,M.; Jorgensen,J.H.;Ferraro, M.J. Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices. Clin. Infect. Dis.2009, 49, 1749–1755. https://doi.org/https://doi.org/10.1086/647952
[25] Bauer, A.W.; Kirby, W.M.M.; Sherris, J.C.; Truck, M. Antibiotic Susceptibility Testing by a Standardized Single Disk Method. Am. J. Clin. Pathol. 1966,45, 493–496.https://doi.org/10.1093/ajcp/45.4_ts.493
[26] Trott, O.; Olson, A.J. AutoDockVina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. J Comp Chem. 2010, 31, 455–461.https://doi.org/10.1002/jcc.21334
[27] Lipinski C.A. Drug-like Properties and the Causes of Poor Solubility and Poor Permeability.J PharmacolToxicol Methods2000, 44, 235–249.https://doi.org/10.1016/S1056-8719(00)00107-6
[28] Veber, D.F.; Johnson, S.R.; Cheng, H.Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates.J Med Chem2002,45, 2615–2623.https://doi.org/10.1021/jm020017n
[29] Payne, D.J.; Gwynn, M.N.; Holmes, D.J.; Pompliano, D.L. Drugs for Bad Bugs: Confronting the Challenges of Antibacterial Discovery. Nat. Rev. Drug Discov.2007,6, 29–40.https://doi.org/10.1038/nrd2201
[30] Forsyth, R.A.; Haselbeck, R.J.; Ohlsen, K.L.; Yamamoto, R.T.; Xu, H.; Trawick, J.D.; Wall, D.; Wang, L.; Brown-Driver, V.; Froelich, J.M. et al. A Genome-Wide Strategy for the Identification of Essential Genes in Staphylococcusaureus. Mol. Microbiol.2002, 43, 1387–1400.https://doi.org/10.1046/j.1365-2958.2002.02832.x
[31] Barker, D.F.; Campbell, A.M. Genetic and Biochemical Characterization of the birAGene and its Product: Evidence for a Direct Role of Biotin Holoenzyme Synthetasein Repression of the Biotin Operon in Escherichia coli. J. Mol. Biol. 1981,146, 469–492.https://doi.org/10.1016/0022-2836(81)90043-7