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image of Synthesis of Phenothiazine Derivatives and their Diverse Biological Activities: A Review

Abstract

The increasing resistance of causative agents to current treatments has made infectious disease management more challenging. Heterocyclic compounds have garnered considerable attention due to their numerous significant medical and biological applications. Research interest in heterocyclic compounds is rapidly increasing due to extensive synthetic studies and their functional utility. Phenothiazine (PTZ), an organic thiazine compound, has a broad range of biological activities, including antimicrobial, antimalarial, antipsychotic, anti-inflammatory, and antiemetic effects. Additionally, modifications to the phenothiazine structure have enhanced its efficacy, making it a potential candidate for addressing drug-resistant infections. This review examines recent synthesis methods, including catalytic and microwave-assisted techniques, which have expanded the applications of phenothiazine derivatives. The article also discusses structure-activity relationships, which help optimize the pharmacological properties of these compounds for future therapeutic use.

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2025-08-25
2025-09-21

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References

  1. Slman D.K. Satar H.A. Ketan Z.A. Jawad A.A. Heterocyclic compounds: A study of its biological activity. Al-Nahrain J. Sci. 2024 27 5 19 24 10.22401/ANJS.27.5.03
    [Google Scholar]
  2. Patnayak S. Heterocyclic compounds: A potential drug and its biological activity: A review. J. Nonlinear Anal. Optim 2024 15 1
    [Google Scholar]
  3. Amin A. Qadir T. Sharma P.K. Jeelani I. Abe H. A review on the medicinal and industrial applications of N-containing heterocycles. Open J. Med. Chem. 2022 16 1 1 27
    [Google Scholar]
  4. Narnaware P.H. Shende P.N. An overview on heterocyclic compounds and their versatile applications. Int. J. Curr. Eng. Sci. Res. 2018 5 4 159 162
    [Google Scholar]
  5. Dze K.C. Samad F. Heterocycles, their synthesis and industrial applications: A review. Int. J. Res. Appl. Sci. Eng. Technol. 2020 8 10 36 56 10.22214/ijraset.2020.31786
    [Google Scholar]
  6. Diaz-Muñoz G. Miranda I.L. Sartori S.K. de Rezende D.C. Alves Nogueira Diaz M. Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review. Chirality 2019 31 10 776 812 10.1002/chir.23103 31418934
    [Google Scholar]
  7. Dove A.P. Pratt R.C. Lohmeijer B.G.G. Culkin D.A. Hagberg E.C. Nyce G.W. Waymouth R.M. Hedrick J.L. N-Heterocyclic carbenes: Effective organic catalysts for living polymerization. Polymer (Guildf.) 2006 47 11 4018 4025 10.1016/j.polymer.2006.02.037
    [Google Scholar]
  8. Abd El-Halim H.F. Mohamed G.G. Anwar M.N. Antimicrobial and anticancer activities of schiff base ligand and its transition metal mixed ligand complexes with heterocyclic base. Appl. Organomet. Chem. 2018 32 1 e3899 10.1002/aoc.3899
    [Google Scholar]
  9. Wojtasik K. Pokladko-Kowar M. Gondek E. Optimization of bulk heterojunction photovoltaic structures with heterocyclic derivatives. Crystals (Basel) 2023 13 5 734 10.3390/cryst13050734
    [Google Scholar]
  10. Leontie L. Danac R. Druta I. Carlescu A. Rusu G.I. Newly synthesized fused heterocyclic compounds in thin films with semiconductor properties. Synth. Met. 2010 160 11-12 1273 1279 10.1016/j.synthmet.2010.03.022
    [Google Scholar]
  11. Minkin V.I. Photo-, thermo-, solvato-, and electrochromic spiroheterocyclic compounds. Chem. Rev. 2004 104 5 2751 2776 10.1021/cr020088u 15137806
    [Google Scholar]
  12. Srividhya D. Manjunathan S. Thirumaran S. Synthesis and characterization of new heterocyclic liquid crystals. J. Chem. 2009 6 3 928 937 10.1155/2009/697928
    [Google Scholar]
  13. Grummt U.W. Weiss D. Birckner E. Beckert R. Pyridylthiazoles: Highly luminescent heterocyclic compounds. J. Phys. Chem. A 2007 111 6 1104 1110 10.1021/jp0672003 17253672
    [Google Scholar]
  14. Tsygankova V.Y. Shtompel O. Romaniuk O. Yaikova M. Hurenko A. Brovarets V. Application of synthetic low molecular weight heterocyclic compounds derivatives of pyrimidine, pyrazole and oxazole in agricultural biotechnology as a new plant growth regulating substances. Int. J. Med. Biotechnol. Genet. 2017 2 2 10 32
    [Google Scholar]
  15. Tsygankova V. Andrusevich Y. Shtompel O. Hurenko A. Solomyannyj R. Mrug G. Brovarets V. Stimulating effect of five- and six-membered heterocyclic compounds on seed germination and vegetative growth of maize (zea mays l.). Int. J. Biol. Res. 2016 1 4 1 14
    [Google Scholar]
  16. Gad M.A. Bakry M.M.S. Tolba E.F.M. Alkhaibari A.M. Mashlawi A.M. Thabet M.A. Al-Taifi E.A. Bakhite E.A. Exploration of some heterocyclic compounds containing trifluoromethylpyridine scaffold as insecticides toward aphis gossypii insects. Chem. Biodivers. 2024 21 6 e202400451 10.1002/cbdv.202400451 38556464
    [Google Scholar]
  17. Fahmy A.F.M. Rizk S.A. Hemdan M.M. El-Sayed A.A. Hassaballah A.I. Efficient green synthesis and computational chemical study of some interesting heterocyclic derivatives as insecticidal agents. J. Heterocycl. Chem. 2018 55 11 2545 2555 10.1002/jhet.3308
    [Google Scholar]
  18. El-Ossaily Y.A. Bakhite E.A.G. Gad M.A. Abdu-Allah H.H.M. Abuelhasan S. Ibrahim O.F. Marae I.S. Althobaiti I.O. Alanazi N.M.M. Al-Muailkel N.S. El-Sayed M.Y. Alanazi M.M. Synthesis, characterization, antibacterial evaluation, and insecticidal activity of some heterocyclic compounds containing styrylpyridine moiety. Russ J. Bioorganic Chem. 2023 49 S1 S159 S170 (Suppl. 1) 10.1134/S1068162023080137
    [Google Scholar]
  19. El-Bana G.G. Abd El Ghani G.E. El-Rokh A.R. Hassanien A.E. Synthesis and insecticidal assessment of some innovative heterocycles incorporating a pyrazole moiety. Polycycl. Aromat. Compd. 2024 44 9 6314 6334
    [Google Scholar]
  20. Anamika A. Utreja D. Kaur J. Sharma S. Synthesis of schiff bases of coumarin and their antifungal activity. Indian J. Heterocycl. Chem. 2018 28 4 433 439
    [Google Scholar]
  21. Chen Y. Liu H. Wang J. Wang K. Zhang Z. He B. Ye Y. Design, synthesis, and antifungal evaluation of diverse heterocyclic hydrazide derivatives as potential succinate dehydrogenase inhibitors. J. Agric. Food Chem. 2024 72 23 12915 12924 10.1021/acs.jafc.3c08927 38807027
    [Google Scholar]
  22. Dawar M. Utreja D. Rani R. Kaur K. Synthesis and evaluation of isatin derivatives as antifungal agents. Lett. Org. Chem. 2020 17 3 199 205 10.2174/1570178616666190724120308
    [Google Scholar]
  23. Kaur G. Utreja D. Kaur J. Synthesis of metal complexes of schiff bases of halogenated anilines and their antifungal activity. Plant Dis. Res. 2017 32 2 228 231
    [Google Scholar]
  24. Goyal A. Utreja D. Garg A. Sharma V.K. Synthesis and antifungal activity of sulfonamides schiff bases and their metal complexes. Agri Res. J. 2018 55 2 377 379
    [Google Scholar]
  25. Kaur L. Utreja D. Dhillon N.K. N-Alkylation of 2-substituted benzimidazole derivatives and their evaluation as antinemic agents. Russ. J. Org. Chem. 2021 57 6 961 967 10.1134/S1070428021060129
    [Google Scholar]
  26. Kaur G. Utreja D. Jain N. Dhillon N.K. Synthesis and evaluation of pyrazole derivatives as potent antinemic agents. Russ. J. Org. Chem. 2020 56 1 113 118 10.1134/S1070428020010182
    [Google Scholar]
  27. Samita; Utreja, D.; Dhillon, N.K. An efficacious protocol for the reduction of benzothiazole using mg/meoh and their antinemic activity against meloidogyne incognita. Russ. J. Bioorganic Chem. 2022 48 1 135 142 10.1134/S1068162022010101
    [Google Scholar]
  28. Jain N. Utreja D. Dhillon N.K. A convenient one pot synthesis and antinemic studies of nicotinic acid derivatives. Russ. J. Org. Chem. 2019 55 845 851 10.1134/S1070428019060150
    [Google Scholar]
  29. Liao A. Sun W. Liu Y. Yan H. Xia Z. Wu J. Pyrrole and pyrrolidine analogs: The promising scaffold in discovery of pesticides. Chin. Chem. Lett. 2024 110094
    [Google Scholar]
  30. Cai Q. Song H. Zhang Y. Zhu Z. Zhang J. Chen J. Quinoline derivatives in discovery and development of pesticides. J. Agric. Food Chem. 2024 72 22 12373 12386 10.1021/acs.jafc.4c01582 38775264
    [Google Scholar]
  31. Ayyad M.A. Ali M.A. Helmy E.T. Soliman U.A. Novel triazole derivatives as potential rodenticides against the Norway rat, R. norvegicus: Histology, biochemical alternations, and field application. Chem. Zvesti 2023 77 10 5947 5959 10.1007/s11696‑023‑02912‑2
    [Google Scholar]
  32. Kaddah M.M. Fahmi A.A. Kamel M.M. Rizk S.A. Ramadan S.K. Rodenticidal activity of some quinoline-based heterocycles derived from hydrazide–hydrazone derivative. Polycycl. Aromat. Compd. 2023 43 5 4231 4241 10.1080/10406638.2022.2088576
    [Google Scholar]
  33. Al-Mulla A. A review: Biological importance of heterocyclic compounds. Pharma Chem. 2017 9 13 141 147
    [Google Scholar]
  34. Salotra R. Utreja D. Sharma P. A convenient one-pot synthesis of chalcones and their derivatives and their antimicrobial activity. Russ. J. Org. Chem. 2020 56 12 2207 2211 10.1134/S1070428020120258
    [Google Scholar]
  35. Priya B. Utreja D. Kalia A. Schiff bases of indole-3-carbaldehyde: Synthesis and evaluation as antimicrobial agents. Russ. J. Bioorganic Chem. 2022 48 6 1282 1290 10.1134/S1068162022060188
    [Google Scholar]
  36. Madhvi; Utreja, D.; Kalia, A. Efficient p-Toluenesulfonic Acid-Catalyzed Synthesis of 5-Aryl-5,10-dihydropyrimido[4,5-b]quinoline-2,4(1H,3H)-diones and Their Antimicrobial Activity. Russ. J. Org. Chem. 2022 58 9 1327 1335 10.1134/S1070428022090196
    [Google Scholar]
  37. Jain P. Utreja D. Sharma P. An efficacious synthesis of n-1, c-3 substituted indole derivatives and their antimicrobial studies. J. Heterocycl. Chem. 2019 57 1 1 8
    [Google Scholar]
  38. Kaur J. Utreja D. Recent developments in the synthesis and antimicrobial activity of indole and its derivatives. Curr. Org. Synth. 2019 16 1 17 37 10.2174/1570179415666181113144939 31965921
    [Google Scholar]
  39. Francescato G. Silva S.M. Leitão M.I.P.S. Gaspar-Cordeiro A. Giannopoulos N. Gomes C.S.B. Pimentel C. Petronilho A. Nickel N‐heterocyclic carbene complexes based on xanthines: Synthesis and antifungal activity on Candida sp. Appl. Organomet. Chem. 2024 38 10 e6687 10.1002/aoc.6687
    [Google Scholar]
  40. Utreja D. Kaur J. Kaur K. Jain P. 1,3,5-Triazine: Synthesis and antibacterial activity. Mini Rev. Org. Chem. 2020 17 1 51 10.2174/1570193X17666200129094032
    [Google Scholar]
  41. Oliveira I.S. Garcia M.S.A. Cassani N.M. Oliveira A.L.C. Freitas L.C.F. Bertolini V.K.S. Castro J. Clauss G. Honorato J. Gadelha F.R. Miguel D.C. Jardim A.C.G. Abbehausen C. Exploring antiviral and antiparasitic activity of gold N-heterocyclic carbenes with thiolate ligands. Dalton Trans. 2024 53 47 18963 18973 10.1039/D4DT01879F 39171417
    [Google Scholar]
  42. Ahmad G. Sohail M. Bilal M. Rasool N. Qamar M.U. Ciurea C. Marceanu L.G. Misarca C. N-Heterocycles as promising antiviral agents: A comprehensive overview. Molecules 2024 29 10 2232 10.3390/molecules29102232 38792094
    [Google Scholar]
  43. Zhao Q. Han B. Peng C. Zhang N. Huang W. He G. Li J.L. A promising future of metal‐ N ‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents. Med. Res. Rev. 2024 44 5 2194 2235 10.1002/med.22039 38591229
    [Google Scholar]
  44. Pal R. Matada G.S.P. Teli G. Saha M. Patel R. Therapeutic potential of anticancer activity of nitrogen-containing heterocyclic scaffolds as Janus kinase (JAK) inhibitor: Biological activity, selectivity, and structure–activity relationship. Bioorg. Chem. 2024 152 107696 10.1016/j.bioorg.2024.107696 39167870
    [Google Scholar]
  45. Kumar S. Singh R.K. Patial B. Goyal S. Bhardwaj T.R. Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria. J. Enzyme Inhib. Med. Chem. 2016 31 2 173 186 10.3109/14756366.2015.1016513 25775094
    [Google Scholar]
  46. Huang Z. Zhang X. Li J. Zhang L. Shen Y. Wang R. Zhang Y. Mao Z. N-Heterocyclic functionalized chalcone derivatives as anti-inflammatory agents for atopic dermatitis treatment by inhibiting JAK1/STAT3 signaling pathway. Bioorg. Chem. 2025 156 108200 10.1016/j.bioorg.2025.108200 39874907
    [Google Scholar]
  47. Sadawarte G.P. Rajput J.D. Kale A.D. Jagrut V.B. Synthesis and biological evaluation of five- and six-membered heterocycles as an anti-diabetic agent: An overview. J. Chem. Rev. 2024 1 331 352
    [Google Scholar]
  48. Kanupriya; Mittal, R.K.; Sharma, V.; Biswas, T.; Mishra, I. Recent advances in nitrogen-containing heterocyclic scaffolds as antiviral agents. Med. Chem. 2024 20 5 487 502 10.2174/0115734064280150231212113012 38279757
    [Google Scholar]
  49. Mallappa C. M., Choudhary, N., Yadav, K.K., Qasim, M.T., Zairov, R., Patel, A., Yadav, V.K., Jangir, M. Recent advances in the synthesis of nitrogen-containing heterocyclic compounds via multicomponent reaction and their emerging biological applications: a review. J. Iran.Chem. Soc 2025 22 1 1 33
    [Google Scholar]
  50. Mosnaim A.D. Ranade V.V. Wolf M.E. Puente J. Antonieta Valenzuela M. Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents. Am. J. Ther. 2006 13 3 261 273 10.1097/01.mjt.0000212897.20458.63 16772768
    [Google Scholar]
  51. Varga B. Csonka Á. Csonka A. Molnár J. Amaral L. Spengler G. Possible biological and clinical applications of phenothiazines. Anticancer Res. 2017 37 11 5983 5993 29061777
    [Google Scholar]
  52. Fiorentino F. Nocentini A. Rotili D. Supuran C.T. Mai A. Antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants potently activate pharmacologically relevant human carbonic anhydrase isoforms II and VII. J. Enzyme Inhib. Med. Chem. 2023 38 1 2188147 10.1080/14756366.2023.2188147 36912265
    [Google Scholar]
  53. Puranik N. Song M. Therapeutic role of heterocyclic compounds in neurodegenerative diseases: Insights from alzheimer’s and parkinson’s diseases. Neurol. Int. 2025 17 2 26 10.3390/neurolint17020026 39997657
    [Google Scholar]
  54. Pyatigorskaya N.V. Brkich G.E. Pavlov A.N. Beregovykh V.V. Evdokimova O.V. A scientific methodology for expansion of anti-Parkinson drug product range. J. Pharm. Sci. Res. 2017 9 9 1561 1563
    [Google Scholar]
  55. Bhatnagar A. Pemawat G. Recent developments of antipsychotic drugs with phenothiazine hybrids: A review. Chem. Biol. Interact. 2022 12 4 77 87
    [Google Scholar]
  56. Rácz B. Spengler G. Repurposing antidepressants and phenothiazine antipsychotics as efflux pump inhibitors in cancer and infectious diseases. Antibiotics (Basel) 2023 12 1 137 10.3390/antibiotics12010137 36671340
    [Google Scholar]
  57. Posso M.C. Domingues F.C. Ferreira S. Silvestre S. Development of phenothiazine hybrids with potential medicinal interest: A review. Molecules 2022 27 1 276 10.3390/molecules27010276 35011508
    [Google Scholar]
  58. Edinoff A.N. Armistead G. Rosa C.A. Anderson A. Patil R. Cornett E.M. Murnane K.S. Kaye A.M. Kaye A.D. Phenothiazines and their evolving roles in clinical practice: A narrative review. Health Psychol. Res. 2022 10 4 38930 10.52965/001c.38930 36425230
    [Google Scholar]
  59. Ohlow M.J. Moosmann B. Phenothiazine: The seven lives of pharmacology’s first lead structure. Drug Discov. Today 2011 16 3-4 119 131 10.1016/j.drudis.2011.01.001 21237283
    [Google Scholar]
  60. Vanneste M. Venzke A. Guin S. Fuller A.J. Jezewski A.J. Beattie S.R. Krysan D.J. Meyers M.J. Henry M.D. The anti-cancer efficacy of a novel phenothiazine derivative is independent of dopamine and serotonin receptor inhibition. Front. Oncol. 2023 13 1295185 10.3389/fonc.2023.1295185 37909019
    [Google Scholar]
  61. Gureev A.P. Sadovnikova I.S. Popov V.N. Molecular mechanisms of the neuroprotective effect of methylene blue. Biochemistry (Mosc.) 2022 87 9 940 956 10.1134/S0006297922090073 36180986
    [Google Scholar]
  62. Lu M. Li J. Luo Z. Zhang S. Xue S. Wang K. Shi Y. Zhang C. Chen H. Li Z. Roles of dopamine receptors and their antagonist thioridazine in hepatoma metastasis. OncoTargets Ther. 2015 8 1543 1552 26124671
    [Google Scholar]
  63. Cantisani C. Ricci S. Grieco T. Paolino G. Faina V. Silvestri E. Calvieri S. Topical promethazine side effects: Our experience and review of the literature. BioMed Res. Int. 2013 2013 1 9 10.1155/2013/151509 24350243
    [Google Scholar]
  64. Rashid M. Rahman M. Khan M.F. Phenothiazines and related antipsychotic drugs. Medicinal Chemistry of Drugs Affecting the Nervous System. Sharjah, UAE Bentham Science Publishers 2020 109 162 10.2174/9789811454073120020005
    [Google Scholar]
  65. Jenkins G. Review of dopamine antagonists for nausea and vomiting in palliative care patients. J. Pain Palliat. Care Pharmacother. 2024 38 1 38 44 10.1080/15360288.2023.2268065 37843383
    [Google Scholar]
  66. Friend D.G. Method for evaluating antipruritic agents Studies on methdilazine. Clin. Pharmacol. Ther. 1961 2 5 605 609 10.1002/cpt196125605 13702065
    [Google Scholar]
  67. Malandain L. Thibaut F. Is there any relevance for the use of cyamemazine in the treatment of schizophrenia? Indian Journal of Private Psychiatry 2023 17 1 14 19 10.5005/jp‑journals‑10067‑0128
    [Google Scholar]
  68. Bari D.G. Saravanan K. Ahmad A. A review on antipsychotics for schizophrenia. Int. J. Pharm. Sci. Res. 2019 10 5234 5251
    [Google Scholar]
  69. Twycross R.G. Barkby G.D. Hallwood P.M. The use of low dose levomepromazine (methotrimeprazine) in the management of nausea and vomiting. Prog. Palliat. Care 1997 5 2 49 53 10.1080/09699260.1997.12098230
    [Google Scholar]
  70. Chouinard G. Samaha A.N. Chouinard V.A. Peretti C.S. Kanahara N. Takase M. Iyo M. Antipsychotic-induced dopamine supersensitivity psychosis: Pharmacology, criteria, and therapy. Psychother. Psychosom. 2017 86 4 189 219 10.1159/000477313 28647739
    [Google Scholar]
  71. Fink M. Effect of anticholinergic agent, diethazine, on EEG and behavior; significance for theory of convulsive therapy. AMA Arch. Neurol. Psychiatry 1958 80 3 380 387 10.1001/archneurpsyc.1958.02340090116017 13570753
    [Google Scholar]
  72. Sydorova N. Class ic antiarrhythmic drugs: Informed choice. Proc. La. Acad. Sci. 2023 77 83 91
    [Google Scholar]
  73. Tenover F.C. Hughes J.M. The challenges of emerging infectious diseases. Development and spread of multiply-resistant bacterial pathogens. JAMA 1996 275 4 300 304 10.1001/jama.1996.03530280052036 8544270
    [Google Scholar]
  74. Khelwati H. van Geelen L. Kalscheuer R. Müller T.J.J. Synthesis, electronic, and antibacterial properties of 3,7-di(hetero)aryl-substituted phenothiazinyl N-propyl trimethylammonium salts. Molecules 2024 29 9 2126 10.3390/molecules29092126 38731617
    [Google Scholar]
  75. El-Sedik M.S. Mohamed M.B.I. Abdel-Aziz M.S. Aysha T.S. Synthesis of new D–π–A phenothiazine-based fluorescent dyes: Aggregation induced emission and antibacterial activity. J. Fluoresc. 2024 1 12 38647963
    [Google Scholar]
  76. Sarhan M.O. Haffez H. Elsayed N.A. El-Haggar R.S. Zaghary W.A. New phenothiazine conjugates as apoptosis inducing agents: Design, synthesis, In-vitro anti-cancer screening and 131I-radiolabeling for in-vivo evaluation. Bioorg. Chem. 2023 141 106924 10.1016/j.bioorg.2023.106924 37871390
    [Google Scholar]
  77. Sudhakar K. Ahamed J.I. Kamalarajan P. Synthesis, spectral characterizations, vibrational spectroscopy, DFT-computations, antibacterial, antioxidant, and molecular docking studies of the novel (Z)-2-(5-((10-hexyl-10H-phenothiazin-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid. J. Mol. Struct. 2023 1292 136008 10.1016/j.molstruc.2023.136008
    [Google Scholar]
  78. Venkatesan K. Satyanarayana V.S.V. Sivakumar A. Synthesis and biological evaluation of novel phenothiazine derivatives as potential antitumor agents. Polycycl. Aromat. Compd. 2023 43 1 850 859 10.1080/10406638.2021.2021254
    [Google Scholar]
  79. Hsu K.C. Chu J.C. Tseng H.J. Liu C.I. Wang H.C. Lin T.E. Lee H.S. Hsin L.W. Wang A.H.J. Lin C.H. Huang W.J. Synthesis and biological evaluation of phenothiazine derivative-containing hydroxamic acids as potent class II histone deacetylase inhibitors. Eur. J. Med. Chem. 2021 219 113419 10.1016/j.ejmech.2021.113419 33845233
    [Google Scholar]
  80. Guguloth V. Thirukovela N.S. Paidakula S. Vadde R. One-pot regioselective synthesis of some novel isoxazole-phenothiazine hybrids and their antibacterial activity. Russ. J. Gen. Chem. 2020 90 3 470 475 10.1134/S1070363220030214
    [Google Scholar]
  81. Moise I.M. Bîcu E. Farce A. Dubois J. Ghinet A. Indolizine-phenothiazine hybrids as the first dual inhibitors of tubulin polymerization and farnesyltransferase with synergistic antitumor activity. Bioorg. Chem. 2020 103 104184 10.1016/j.bioorg.2020.104184 32891861
    [Google Scholar]
  82. Luan Y. Liu J. Gao J. Wang J. The design and synthesis of novel phenothiazine derivatives as potential cytotoxic agents. Lett. Drug Des. Discov. 2019 17 1 57 67 10.2174/1570180816666181115112236
    [Google Scholar]
  83. Ahamed J.I. Valan M.F. Pandurengan K. Agastian P. Venkatadri B. Rameshkumar M.R. Narendran K. A novel method for the synthesis and characterization of 10-hexyl-3-(1-hexyl-4, 5-diphenyl-1H-imidazol-2-yl)-10H-phenothiazine: DFT computational, in vitro anticancer and in silico molecular docking studies. Res. Chem. Intermed. 2021 47 2 759 794 10.1007/s11164‑020‑04297‑3
    [Google Scholar]
  84. Shanmugam S. Neelakandan K. Gopalakrishnan M. Pazhamalai S. Design, synthesis, characterization and biological evaluation of some 2-(E)-(N-(azobenzyl)-4-iminoethan-1-yl)-10H-phenothiazines. Mater. Today Proc. 2021 42 989 1001 10.1016/j.matpr.2020.11.979
    [Google Scholar]
  85. Sivaramakarthikeyan R. Karuppasamy A. Iniyaval S. Padmavathy K. Lim W.M. Mai C.W. Ramalingan C. Phenothiazine and amide-ornamented novel nitrogen heterocyclic hybrids: Synthesis, biological and molecular docking studies. New J. Chem. 2020 44 10 4049 4060 10.1039/C9NJ05489H
    [Google Scholar]
  86. Shanti D. Design, synthesis and bio-evaluation of new phenothiazine derivatives of sulfonamide dyes as anticancer agents. Adv. Mater. Process. 2020 5 3 1 6
    [Google Scholar]
  87. Sellamuthu S. Kumar A. Nath G. Singh S.K. Design, synthesis and biological profiling of novel phenothiazine derivatives as potent antitubercular agents. Antiinfect. Agents 2018 16
    [Google Scholar]
  88. Reddyrajula R. Dalimba U. Madan Kumar S. Molecular hybridization approach for phenothiazine incorporated 1,2,3-triazole hybrids as promising antimicrobial agents: Design, synthesis, molecular docking and in silico ADME studies. Eur. J. Med. Chem. 2019 168 263 282 10.1016/j.ejmech.2019.02.010 30822714
    [Google Scholar]
  89. Bayoumy N.M. Fekri A. Tawfik E.H. Fadda A.A. Synthesis, characterization and antimicrobial evaluation of some new heterocycles incorporating phenothiazine moiety. Polycycl. Aromat. Compd. 2021 41 5 982 991 10.1080/10406638.2019.1636832
    [Google Scholar]
  90. Sachdeva T. Low M.L. Mai C.W. Cheong S.L. Liew Y.K. Milton M.D. Design, synthesis and characterisation of novel phenothiazine‐based triazolopyridine derivatives: Evaluation of anti‐breast cancer activity on human breast carcinoma. ChemistrySelect 2019 4 43 12701 12707 10.1002/slct.201903203
    [Google Scholar]
  91. Liu N. Jin Z. Zhang J. Jin J. Antitumor evaluation of novel phenothiazine derivatives that inhibit migration and tubulin polymerization against gastric cancer MGC-803 cells. Invest. New Drugs 2019 37 1 188 198 10.1007/s10637‑018‑0682‑x 30345465
    [Google Scholar]
  92. Gul H.I. Yamali C. Gunesacar G. Sakagami H. Okudaira N. Uesawa Y. Kagaya H. Cytotoxicity, apoptosis, and QSAR studies of phenothiazine derived methoxylated chalcones as anticancer drug candidates. Med. Chem. Res. 2018 27 10 2366 2378 10.1007/s00044‑018‑2242‑5
    [Google Scholar]
  93. Zhang J.X. Guo J.M. Zhang T.T. Lin H.J. Qi N.S. Li Z.G. Zhou J.C. Zhang Z.Z. Antiproliferative phenothiazine hybrids as novel apoptosis inducers against MCF-7 breast cancer. Molecules 2018 23 6 1288 10.3390/molecules23061288 29843370
    [Google Scholar]
  94. Venkatesan K. Satyanarayana V.S.V. Sivakumar A. Efficient synthesis of phenothiazine-based heterocyclic derivatives and their biological studies. Indian J. Heterocycl. Chem. 2018 28 03 367 372
    [Google Scholar]
  95. Sharma M.K. Machhi J. Murumkar P. Yadav M.R. New role of phenothiazine derivatives as peripherally acting CB1 receptor antagonizing anti-obesity agents. Sci. Rep. 2018 8 1 1650 10.1038/s41598‑018‑20078‑w 29374224
    [Google Scholar]
  96. Brem B. Gal E. Găină L. Silaghi-Dumitrescu L. Fischer-Fodor E. Tomuleasa C.I. Grozav A. Zaharia V. Filip L. Cristea C. Novel thiazolo[5,4-b] phenothiazine derivatives: Synthesis, structural characterization, and in vitro evaluation of antiproliferative activity against human leukemia. Int. J. Mol. Sci. 2017 18 7 1365 10.3390/ijms18071365 28672876
    [Google Scholar]
  97. Ghorab M.M. Alsaid M.S. Samir N. Abdel-Latif G.A. Soliman A.M. Ragab F.A. Abou El Ella D.A. Aromatase inhibitors and apoptotic inducers: Design, synthesis, anticancer activity and molecular modeling studies of novel phenothiazine derivatives carrying sulfonamide moiety as hybrid molecules. Eur. J. Med. Chem. 2017 134 304 315 10.1016/j.ejmech.2017.04.028 28427017
    [Google Scholar]
  98. Ma X.H. Liu N. Lu J.L. Zhao J. Zhang X.J. Design, synthesis and antiproliferative activity of novel phenothiazine-1,2,3-triazole analogues. J. Chem. Res. 2017 41 12 696 698 10.3184/174751917X15122516000140
    [Google Scholar]
  99. Fu D.J. Zhao R.H. Li J.H. Yang J.J. Mao R.W. Wu B.W. Li P. Zi X.L. Zhang Q.Q. Cai H.J. Zhang S.Y. Zhang Y.B. Liu H.M. Molecular diversity of phenothiazines: Design and synthesis of phenothiazine–dithiocarbamate hybrids as potential cell cycle blockers. Mol. Divers. 2017 21 4 933 942 10.1007/s11030‑017‑9773‑4 28785928
    [Google Scholar]
  100. Ghinet A. Moise I.M. Rigo B. Homerin G. Farce A. Dubois J. Bîcu E. Studies on phenothiazines: New microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents. Bioorg. Med. Chem. 2016 24 10 2307 2317 10.1016/j.bmc.2016.04.001 27073050
    [Google Scholar]
  101. Ramprasad J. Nayak N. Dalimba U. Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents. Eur. J. Med. Chem. 2015 106 75 84 10.1016/j.ejmech.2015.10.035 26520841
    [Google Scholar]
  102. He C.X. Meng H. Zhang X. Cui H.Q. Yin D.L. Synthesis and bio-evaluation of phenothiazine derivatives as new anti-tuberculosis agents. Chin. Chem. Lett. 2015 26 8 951 954 10.1016/j.cclet.2015.03.027
    [Google Scholar]
  103. Zhi S. Mu S. Liu Y. Gong M. Wang P.B. Liu D.K. Synthesis and biological evaluation of novel phenothiazine derivatives as non-peptide arginine vasopressin V2 receptor antagonists. Chin. Chem. Lett. 2015 26 5 627 630 10.1016/j.cclet.2015.01.022
    [Google Scholar]
  104. Maddila S. Momin M. Gorle S. Palakondu L. Jonnalagadda S.B. Synthesis and antioxidant evaluation of novel phenothiazine-linked substituted benzylideneamino-1,2,4-triazole derivatives. J. Chil. Chem. Soc. 2015 60 2 2919 2923 10.4067/S0717‑97072015000200012
    [Google Scholar]
  105. Bansode T.N. Rangari R.P. Shimpi P.A. Synthesis and biological evaluation of some novel 6-(substituted-phenyl)-4-(10H-phenothiazin-10-yl)-pyrimidin-2-(1H)-ones/thiones. Pharm. Chem. J. 2014 48 7 430 433 10.1007/s11094‑014‑1125‑4
    [Google Scholar]
  106. Siddiqui A.B. Trivedi A.R. Kataria V.B. Shah V.H. 4,5-Dihydro-1H-pyrazolo[3,4-d]pyrimidine containing phenothiazines as antitubercular agents. Bioorg. Med. Chem. Lett. 2014 24 6 1493 1495 10.1016/j.bmcl.2014.02.012 24582983
    [Google Scholar]
  107. Dunn E.A. Roxburgh M. Larsen L. Smith R.A.J. McLellan A.D. Heikal A. Murphy M.P. Cook G.M. Incorporation of triphenylphosphonium functionality improves the inhibitory properties of phenothiazine derivatives in Mycobacterium tuberculosis. Bioorg. Med. Chem. 2014 22 19 5320 5328 10.1016/j.bmc.2014.07.050 25150092
    [Google Scholar]
  108. Priyadarshan A. Tripathi G. Singh A.K. Rajkhowa S. Kumar A. Tiwari V.K. Solvent-free approaches towards the synthesis of therapeutically important heterocycles. Curr. Green Chem. 2024 11 2 127 147 10.2174/2213346110666230915163034
    [Google Scholar]
  109. Martelli L.S.R. Machado I.V. dos Santos J.R.N. Corrêa A.G. Greener asymmetric organocatalysis using bio-based solvents. Catalysts 2023 13 3 553 10.3390/catal13030553
    [Google Scholar]
  110. Swami R. Yadav J. Kumar S. Gaba M. Recent advances in microwave-assisted synthesis of triazoles: A greener approach. RSC Advances 2025 15 4223 4242 10.1039/D4RA06886F
    [Google Scholar]
  111. Peshkov V.A. Pereshivko O.P. Van der Eycken E.V. Ultrasonication as a tool for green organic synthesis. ChemSusChem 2023 16 e202300684
    [Google Scholar]
  112. Al Zahrani N.A. El-Shishtawy R.M. Elaasser M.M. Asiri A.M. Synthesis of novel chalcone-based phenothiazine derivatives as antioxidant and anticancer agents. Molecules 2020 25 19 4566 10.3390/molecules25194566 33036301
    [Google Scholar]
  113. Venkatesan K. Satyanarayana V.S.V. Sivakumar A. Ramamurthy C. Thirunavukkarusu C. Synthesis, spectral characterization and antitumor activity of phenothiazine derivatives. J. Heterocycl. Chem. 2020 57 7 2722 2728 10.1002/jhet.3980
    [Google Scholar]
  114. Andac A.C. Facile microwave synthesis of a novel phenothiazine derivative and its cytotoxic activity. Organic Communications 2020 13 4 175 183 10.25135/acg.oc.86.20.10.1853
    [Google Scholar]
  115. Alsharekh M.M. Althagafi I.I. Shaaban M.R. Farghaly T.A. Microwave-assisted and thermal synthesis of nanosized thiazolyl-phenothiazine derivatives and their biological activities. Res. Chem. Intermed. 2019 45 2 127 154 10.1007/s11164‑018‑3594‑7
    [Google Scholar]
  116. Pemmadi R.V. Kurre P.N. Guruvelli P.V.S. Jamullamudi R.N. Muthyala M.K.K. Microwave-assisted synthesis and SAR studies of novel hybrid phenothiazine analogs as potential antitubercular agents. Indian J. Chem. B 2018 57B 556 566
    [Google Scholar]
  117. Venkatesan K. Satyanarayana V.S.V. Mohanapriya K. Khora S.S. Sivakumar A. Ultrasound-mediated synthesis of phenothiazine derivatives and their in vitro antibacterial and antioxidant studies. Res. Chem. Intermed. 2015 41 2 595 607 10.1007/s11164‑013‑1213‑1
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575405792250813070957
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Synthesis of Phenothiazine Derivatives and their Diverse Biological Activities: A Review
Bentham Science Publishers ; https://doi.org/10.2174/0113895575405792250813070957
/content/journals/mrmc/10.2174/0113895575405792250813070957
/content/journals/mrmc/10.2174/0113895575405792250813070957
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  • Article Type:     Review Article
Keywords: phenothiazine ; antibacterial ; Heterocyclic compounds ; antimicrobial ; anti-parkinson

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