Anti-Alzheimer’s and Anti-Fungal Activities of Pyrrolo[1,2-a] Quinoline Derivatives

Pharmaceutical Science-Chemistry

Authors

  • Pramod N Patil Department of Chemistry, Rani Channamma University, Belagavi, Karnataka, India- 591156.
  • Vijayakumar Uppar Honeychem Pharma Research Pvt. LTD., Peenya Industrial Estate, Bangalore, Karnataka, India- 560058.
  • Basavaraj Padmashali Department of Chemistry, Rani Channamma University, Belagavi, Karnataka, India- 591156 https://orcid.org/0000-0003-3670-5101
  • Rangappa Keri Centre for Nano and Material Sciences, Jain (Deemed-to-be University), Jain Global Campus, Kanakapura, Bangalore, Karnataka, India– 562112

DOI:

https://doi.org/10.22376/ijlpr.2023.13.6.P1-P11

Keywords:

Alzheimer’s, dipolarophile, dimethyl acetylene dicarboxylate, neurologic, physiological dysfunction, ethyl propiolate, psychiatrists

Abstract

Psychiatrists have described the protein deposits in the brain that causes various diseases such as cerebral, functional,physiological dysfunction, and neurodegenerative diseases. Although Alzheimer's disease is detectable, its treatment remainsunattainable. More than 4.6 million new patients are recorded yearly, who are affected by Alzheimer's disease and only a fewdrugs are currently in use for treatment with side effects. Hence, there is a clinical need for new drugs, design, and development.On the other hand, despite the development of antifungal therapeutics over the last three decades, antifungal resistance is still amajor cause. Regularly using inappropriate antimicrobials has become a major healthcare problem globally in the 21st century andhas been titled a "silent tsunami facing modern medicine." It has been estimated that over 8,000,000 die yearly, which providesscope for developing novel antifungal drugs. In this research paper, we describe the synthesized dimethyl-1-(4-substitutedbenzoyl)-5-methylpyrrolo[1,2-a] quinoline-2,3-dicarboxylate 1a-c and ethyl-1-(4-substituted benzoyl) 5-methylpyrrolo[1,2-a]quinoline-3-carboxylate 1d-f were evaluated for in vitro antifungal and anti-Alzheimer’s activities. The derivatives1a-f wereobtained by 1,3-dipolar cycloaddition reaction by treating quaternary salt with dimethyl acetylene dicarboxylate and ethylpropiolate respectively, in the presence of K2CO3 and DMF as a solvent. Among all compounds, 1a, 1d, and 1e showed thehighest inhibitory capacity with IC50 values of 0.28, 0.32, and 0.30 μM, respectively. On the other hand, derivatives were alsoscreened for antifungal activity that displayed moderate activity, whereas 1a and 1f derivatives showed good activity.

References

Goedert M, Spillantini MG. A century of Alzheimer’s disease. Science. 2006;314(5800):777-81. doi 10.1126/science.1132814, PMID 17082447.

Erik D, Roberson LM. 100 years and counting: prospects for defeating. J Alzheimers Dis. 2006;314:781.

Kosyreva AM, Sentyabreva AV, Tsvetkov IS, Makarova OV. Alzheimer’s disease and inflammation. Brain Sci. 2022;12(9):1237. doi: 10.3390/brainsci12091237, PMID 36138973.

Zeinab B, Rafik K. Comprehensive review on Alzheimer’s disease: causes and treatment. 2020;25:5789.

De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV. Alzheimer’s disease. Sub-Cell Biochem. 2012;65:329-52.

Cipriani G, Dolciotti C, Picchi L, Bonuccelli U. Alzheimer, and his disease: A brief history. Neurol Sci. 2011;32(2):275-9. doi: 10.1007/s10072-010-0454-7, PMID 21153601.

Terry RD, Davies P. Dementia of the Alzheimer type. Annu Rev Neurosci. 1980;3:77-95. doi: 10.1146/annurev.ne.03.030180.000453, PMID 6251745.

Rathmann KL, Conner CS. Alzheimer’s disease: clinical features, pathogenesis, and treatment. Drug Intell Clin Pharm. 1984;18(9):684-91. doi: 10.1177/106002808401800902, PMID 6383752.

Schachter AS, Davis KL. Alzheimer’s disease. Dialogues Clin Neurosci. 2000;2(2):91-100. doi: 10.31887/DCNS.2000.2.2/asschachter, PMID 22034442.

Neugroschl J, Wang S. Alzheimer’s disease: diagnosis and treatment across the spectrum of disease severity, Mt. Sinai. J Med. 2011;78(Y):596-612.

Tortorano AM, Biraghi E, Astolfi A, Ossi C, Tejada M, Farina C et al. European Confederation of Medical Mycology (ECMM) prospective survey of candidaemia: report from one Italian region. J Hosp Infect. 2002;51(4):297-304. doi: 10.1053/jhin.2002.1261, PMID 12183145.

Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer S, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis. 2003;37(9):1172-7. doi: 10.1086/378745, PMID 14557960.

Iwata K. Drug resistance in human pathogenic fungi. Eur J Epidemiol. 1992;8(3):407-21. doi: 10.1007/BF00158576, PMID 1397205.

Ismail MM, Othmana MH, Mahross MAM, Gad-Elkareema MR, Neelutpal G, Dipak KA et al. Toward a treatment of antibacterial and antifungal infections: design, synthesis and in vitro activity of novel arylhydrazothiazolylsulfonamides analogs and their insight of DFT, docking and molecular dynamic simulations. J Mol Struct. 2021:130862.

Soumen S, Krishnendu B, Swapnadeep J, Jana U. Synthesis of structurally diverse polyfunctional pyrrolo[1,2-a]quinolines by sequential iron-catalyzed three-component coupling and gold-catalyzed hydroarylation reactions. Eur J Org Chem. 2013;27:6055-61.

Liu Y, Zhang Y, Shen YM, Hu HW, Xu JH. Regioselective synthesis of 3-acylindolizines and benzo- analogs via 1,3-dipolar cycloadditions of N-ylides with maleic anhydride. Org Biomol Chem. 2010;8(10):2449-56. doi: 10.1039/c000277a, PMID 20448905.

Sharma V, Kumar V. Indolizine: A biologically active moiety. Med Chem Res. 2014;23(8):3593-606. doi: 10.1007/s00044-014-0940-1.

Meléndez Gómez CMM, Kouznetsov VV, Sortino MA, Álvarez SL, Zacchino SA. In vitro, antifungal activity of polyfunctionalized 2-(hetero) aryl quinolines prepared through imino Diels–Alder reactions. Bioorg Med Chem. 2008;16(17):7908-20. doi: 10.1016/j.bmc.2008.07.079, PMID 18752959.

Vemula VR, Vurukonda S, Bairi CK. Indolizine derivatives: recent advances and potential pharmacological activities. Int J Pharm Sci Rev Res. 2011;11:159-63.

Uppar V, Chandrashekharappa S, Basarikatti AI, Banuprakash G, Mohan M, Chougala M et al. Synthesis, antibacterial, and antioxidant studies of 7-amino-3-(4-fluorobenzoyl)indolizine-1-carboxylate derivatives. J app pharm sci. 2020;10(2):77-85. doi: 10.7324/JAPS.2020.102013.

Uppar V, Chandrashekharappa S, Venugopala KN, Deb PK, Kar S, Alwassil OI et al. Synthesis and characterization of pyrrolo[1,2-a]quinoline derivatives for their larvicidal activity against Anopheles arabiensis. Struct Chem. 2020;31(4):1533-43. doi: 10.1007/s11224-020-01516-w.

Dillard RD, Pavey DE, Benslay DN. Synthesis and antiinflammatory activity of some 2,2-dimethyl-1,2-dihydroquinolines. J Med Chem. 1973;16(3):251-3. doi: 10.1021/jm00261a019, PMID 4733107.

21. Sechi M, Rizzi G, Bacchi A, Carcelli M, Rogolino D, Pala N et al. Design and synthesis of novel dihydroquinoline-3-carboxylic acids as HIV-1 integrase inhibitors. Bioorg Med Chem. 2009;17(7):2925-35. doi: 10.1016/j.bmc.2008.10.088, PMID 19026554.

Testa ML, Lamartina L, Mingoia F. A new entry to the substituted pyrrolo[3,2-c]quinoline derivatives of biological interest by intramolecular heteroannulation of internal imines. Tetrahedron. 2004;60(28):5873-80. doi: 10.1016/j.tet.2004.05.047.

Martins C, Carreiras MC, León R, de los Ríos CDL, Bartolini M, Andrisano V et al. Synthesis and biological assessment of diversely substituted furo[2,3-b]quinolin-4-amine and pyrrolo[2,3-b]quinolin-4-amine derivatives as novel tacrine analogs. Eur J Med Chem. 2011;46(12):6119-30. doi: 10.1016/j.ejmech.2011.09.038, PMID 22000936.

Venugopala NK, Uppar V, Chandrashekharappa S, Abdallah HH, Pillay M, Deb PK et al. Antibiotics. 2020;9.

Clinical microbiology procedures handbook. Henry D Isenberg. Vol. 1. Washington, DC: American Society for Microbiology; 1992.

Ellman GL, Courtney KD, Andres VJ, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88-95. doi: 10.1016/0006-2952(61)90145-9, PMID 13726518.

Asha M, Sílvia C, Rangappa SK. Multi-targeting tacrine conjugates with cholinesterase and amyloid-beta inhibitory activities: new anti-Alzheimer’s agents. Chem Biodivers. 2021;18:e2000083.

Uppar V, Chandrashekharappa S, Shivamallu C, Sushma P, Kollur S, Ortega-Castro J et al. AA, Elgorban AM, Syed A, Kiran KM, Padmashali B, Daniel G, Investigation of Antifungal Properties of Synthetic Dimethyl-4-Bromo-1-(Substituted Benzoyl) Pyrrolo[1,2-a] Quinoline-2,3-Dicarboxylates Analogues: Molecular Docking Studies and Conceptual DFT-Based Chemical Reactivity Descriptors and Pharmacokinetics Evaluation. Molecules, 2021, 26(9), 2722.

Farah H, Ech-chahad A, Lamiri A. New synthesis and biological screening of some pyrrolo quinoline derivatives. 2014;6:63-9.

Isaivani D, Vediappen P, Kumaresan G, Karthikeyan S. A-one Pot Four Component and Microwave-Assisted Synthesis of pyrrole [1, 10]phenanthrolines, Biological Chemistry & Chemical Biology, Chemistry Select. 2017;2:6154.

Faghih-Mirzaei E, Seifi M, Abaszadeh M, Zomorodian K, Helali H. Design, synthesis, biological evaluation and molecular modeling study of novel indolizine-1-carbonitrile derivatives as potential anti-microbial agents. Iran J Pharm Res. 2018;17(3):883-95. PMID 30127812.

Somagond SM, Kamble RR, Kattimani PP, Joshi SD, Dixit SR. Design, synthesis, docking, and in vitro antifungal study of 1,2,4-triazole hybrids of 2-(aryloxy)quinolines. Heterocycl Commun. 2017;23(4):317-24. doi: 10.1515/hc-2016-0073.

Sheng-Qiang W, Yan-Fang W, Zhi X. Tetrazole hybrids and their antifungal activities. 2019;170:225.

Desai NC, Patel BY, Dave BP. Synthesis and antimicrobial activity of novel quinoline derivatives bearing pyrazoline and pyridine analogs. Med Chem Res. 2017;26(1):109-19. doi: 10.1007/s00044-016-1732-6.

Isaivani D, Vediappen P, Kumaresan G, Karthikeyan S. A-one Pot Four Component and Microwave-Assisted Synthesis of pyrrole [1, 10]phenanthrolines, Chemistry Select. 2017;2(6154):6158.

Mostafa M, Abdelgalil YA, Ammar GAM, Elhag A, Ali Kh. Ali, Ahmed R, A novel of quinoxaline derivatives tagged with pyrrolidinyl scaffold as a new class of antimicrobial agents: design, synthesis, antimicrobial activity, and molecular docking simulation. J Mol Struct. 2023;1274:134443.

Appna NR, Nagiri RK, Korupolu RB, Kanugala S, Chityal GK, Thipparapu G et al. Design and synthesis of novel 4-hydrazone functionalized/1,2,4-triazole fused pyrido[2,3-d]pyrimidine derivatives, their evaluation for antifungal activity and docking studies. Med Chem Res. 2019;28(9):1509-28. doi: 10.1007/s00044-019-02390-w.

Najafi Z, Saeedi M, Mahdavi M, Sabourian R, Khanavi M, Tehrani MB, et al. Design and synthesis of novel anti-Alzheimer's agents: acridine-chromenone and quinoline-chromenone hybrids. Bioorg Chem. 2016;67:84-94. doi: 10.1016/j.bioorg.2016.06.001, PMID 27289559.

McKenna MT, Proctor GR, Young LC, Harvey AL. Novel tacrine analogs for potential use against Alzheimer's disease: potent and selective acetylcholinesterase inhibitors and 5-HT uptake inhibitors. J Med Chem. 1997;40(22):3516-23. doi: 10.1021/jm970150t, PMID 9357518.

Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer’s disease. Arch Pharm Res. 2013;36(4):375-99. doi: 10.1007/s12272-013-0036-3, PMID 23435942.

Carla M, Carmo M C, Rafael L, Cristóbal lR, Manuela B, Vincenza A, Isabel I, Ignacio M, Enrique G, Manuela G, Javier E, Abdelouhaid S, Mourad C, Marco-Contelles J, Synthesis and biological assessment of diversely substituted furo[2,3-b]quinolin-4-amine and pyrrolo[2,3-b]quinolin-4-amine derivatives, as novel tacrine analogues, European Journal of Medicinal Chemistry, 2011, 46, 6119.

Mohamed M, Wissam HF, Wassim NS, Costantine FD, Tamer MI, Hanan MR. Synthesis, Synthesis, biological evaluation, and modeling of hybrids from tetrahydro1H-pyrazolo[3,4-b]quinolines as dual cholinesterase and COX-2 inhibitors. Bioorg Chem. 2020;100:103895.

Mroueh M, Faour WH, Shebaby WN, Daher CF, Ibrahim TM, Ragab HM. Synthesis, biological evaluation, and modeling of hybrids from tetrahydro-1H-pyrazolo[3,4-b]quinolines as dual cholinesterase and COX-2 inhibitors. Bioorg Chem. 2020;100:103895. doi: 10.1016/j.bioorg.2020.103895, PMID 32413626.

Mourad C, Eleonora B, Ignacio M, Isabel I, Maciej M, Artur W et al. Krzysztof JK, Carlos M, Marco-Contelles. J, Manuela B, Tacripyrimidines, the first tacrine-dihydropyrimidine hybrids, as multi-target-directed ligands for Alzheimer's disease. Eur J Med Chem. 2018;155:839.

Najafi Z, Mahdavi M, Saeedi M, Karimpour-Razkenari E, Asatouri R, Vafadarnejad F et al. Novel tacrine-1,2,3-triazole hybrids: in vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors. Eur J Med Chem. 2017; 125:1200-12. doi: 10.1016/j.ejmech.2016.11.008, PMID 27863370.

Reddy MVK, Rao KY, Anusha G, Kumar GM, Damu AG, Reddy KR et al. In-vitro evaluation of antioxidant and anticholinesterase activities of novel pyridine, quinoxaline and s-triazine derivatives. Environ Res. 2021; 199:111320. doi: 10.1016/j.envres.2021.111320, PMID 33991570.

Michele P, Emilio L, Ángela R, Begoña G, José A, Aínsa CMM et al. Discovery of 3H-pyrrolo[2,3-c]quinolines with activity against Mycobacterium tuberculosis by allosteric inhibition of the glutamate-5-kinase enzyme. Eur J Chem. 2022; 232:114206.

Published

2023-11-01

How to Cite

N Patil, P., Uppar, V., Padmashali, B., & Keri, R. (2023). Anti-Alzheimer’s and Anti-Fungal Activities of Pyrrolo[1,2-a] Quinoline Derivatives: Pharmaceutical Science-Chemistry. International Journal of Life Science and Pharma Research, 13(6), P1-P11. https://doi.org/10.22376/ijlpr.2023.13.6.P1-P11

Issue

Section

Research Articles