ABSTRACT:

Secondary metabolites comprise a major class of compounds, among which alkaloids are one of the most important due to their diverse structures and wide spectrum of biological activities. While these nitrogen-containing compounds are mainly extracted from plants, they have been known to be useful in the synthesis of a large variety of analogues with applications as pharmaceuticals, for example analgesics, antineoplastic agents, and antimicrobial drugs. A complete and detailed knowledge of alkaloids’ structures and classifications is crucial for efforts in drug discovery and development because quite often the structural features are also associated with their biological activities. Alkaloids are a large and complex group of natural compounds that are characterized by a nitrogenous base. Much has been said about their importance when derived from different plant species on the wide spectrum of pharmacological effects. This literature review paper will attempt to synthesize recent findings pertaining to alkaloids’ clinical importance in modern-day therapeutics and medicine, critically analyzing their traditional and potential contemporary medicinal uses, further indicating the existing lacunae of knowledge and scopes for future study.

REFERENCES :

1) Al‐Mourabit, A.., Zancanella, Manuel., Tilvi, Supriya., & Romo, D.. (2011). Biosynthesis, asymmetric synthesis, and pharmacology, including cellular targets, of the pyrrole-2-aminoimidazole marine alkaloids. Natural product reports , 28 7 , 1229-60 . http://doi.org/10.1039/c0np00013b
2) Bates, Darcy J. P.., & Eastman, A.. (2017). Microtubule destabilising agents: far more than just antimitotic anticancer drugs. British Journal of Clinical Pharmacology , 83 , 255 – 268 . http://doi.org/10.1111/bcp.13126
3) Bhambhani, S.., Kondhare, K. R.., & Giri, A.. (2021). Diversity in Chemical Structures and Biological Properties of Plant Alkaloids. Molecules , 26 . 

http://doi.org/10.3390/molecules26113374
4) Boozari, Motahareh., & Hosseinzadeh, H.. (2020). Natural products for COVID‐19 prevention and treatment regarding to previous coronavirus infections and novel studies. Phytotherapy Research , 35 , 864 – 876 . http://doi.org/10.1002/ptr.6873
5) Chan, E.., Lye, P.., & Wong, S.. (2016). Phytochemistry, pharmacology, and clinical trials of Morus alba.. Chinese journal of natural medicines , 14 1 , 17-30 . http://doi.org/10.3724/SP.J.1009.2016.00017
6) Chrzanowska, M.., Grajewska, Agnieszka., & Rozwadowska, M.. (2016). Asymmetric Synthesis of Isoquinoline Alkaloids: 2004-2015.. Chemical reviews , 116 19 , 12369-12465 . http://doi.org/10.1021/ACS.CHEMREV.6B00315
7) Dührkop, Kai., Nothias, Louis-Félix., Fleischauer, Markus., Reher, R.., Ludwig, M.., Hoffmann, Martin A.., Petráš, D.., Gerwick, W.., Rousu, Juho., Dorrestein, P.., & Böcker, Sebastian. (2020). Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra. Nature Biotechnology , 39 , 462 – 471 . http://doi.org/10.1038/s41587-020-0740-8
8) El‐Seedi, H.., El-Shabasy, Rehan M.., Khalifa, S.., Saeed, A.., Shah, Afzal., Shah, R.., Iftikhar, F.., Abdel-Daim, Mohamed M.., Omri, A.., Hajrahand, Nahid H.., Sabir, J.., Zou, Xiaobo., Halabi, M. F.., Sarhan, W.., & Guo, Weisheng. (2019). Metal nanoparticles fabricated by green chemistry using natural extracts: biosynthesis, mechanisms, and applications. RSC Advances , 9 , 24539 – 24559 . http://doi.org/10.1039/c9ra02225b
9) Hal, S. J.., Lodise, T.., & Paterson, D.. (2012). The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis.. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 54 6 , 755-71 . http://doi.org/10.1093/cid/cir935
10) Hemby, S.., McIntosh, S.., León, F.., Cutler, S.., & McCurdy, C.. (2018). Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7‐hydroxymitragynine. Addiction Biology , 24 , 874 – 885 . http://doi.org/10.1111/adb.12639
11) Huang, Peng., Zhang, Yan., Xiao, Kangpeng., Jiang, Fan., Wang, Hengchao., Tang, Dazhi., Liu, Dan., Liu, Bo., Liu, Yisong., He, Xi., Liu, Hua., Liu, Xiubin., Qing, Z.., Liu, Conghui., Huang, Jialu., Ren, Yuwei., Yun, Long., Yin, Lijuan., Lin, Q.., Zeng, C.., Su, X.., Yuan, Jingyang., Lin, Li., Hu, Nan-Xi., Cao, H.., Huang, Sanwen., Guo, Yuming., Fan, Wei., & Zeng, J.. (2018). The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids. Microbiome , 6 . http://doi.org/10.1186/s40168-018-0590-5
12) Hussain, G.., Rasul, A.., Anwar, H.., Aziz, Nimra., Razzaq, Aroona., Wei, Wei., Ali, Muhammad., Li, Jiang., & Li, Xiaomeng. (2018). Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders. International Journal of Biological Sciences , 14 , 341 – 357 . http://doi.org/10.7150/ijbs.23247
13) Kahl, B.., Becker, K.., & Löffler, B.. (2016). Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections. Clinical Microbiology Reviews , 29 , 401 – 427 . http://doi.org/10.1128/CMR.00069-15
14) Kim, Hyun Woo., Wang, Mingxun., Leber, Christopher A.., Nothias, Louis-Félix., Raphael, ., Reher, ., Kang, K.., Hooft, J. J.., Dorrestein, P.., William, H.., Gerwick, ., & Cottrell, G.. (2020). NPClassifier: A Deep Neural Network-Based Structural Classification Tool for Natural Products. Journal of Natural Products , 84 , 2795 – 2807 . http://doi.org/10.26434/chemrxiv.12885494.v1
15) Kohnen-Johannsen, Kathrin Laura., & Kayser, O.. (2019). Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production. Molecules , 24 . http://doi.org/10.3390/molecules24040796
16) Kruegel, Andrew C.., Gassaway, Madalee., Kapoor, Abhijeet., Váradi, A.., Majumdar, S.., Filizola, M.., Javitch, J.., & Sames, D.. (2016). Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.. Journal of the American Chemical Society , 138 21 , 6754-64 . http://doi.org/10.1021/jacs.6b00360
17) Mokhber-Dezfuli, Najmeh., Saeidnia, S.., Gohari, A.., & Kurepaz-mahmoodabadi, Mahdieh. (2014). Phytochemistry and Pharmacology of Berberis Species. Pharmacognosy Reviews , 8 , 8 – 15 . http://doi.org/10.4103/0973-7847.125517
18) Moloudizargari, Milad., Mikaili, P.., Aghajanshakeri, S.., Asghari, M.., & Shayegh, J.. (2013). Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. Pharmacognosy Reviews , 7 , 199 – 212 . http://doi.org/10.4103/0973-7847.120524
19) Moreira, Rute., Pereira, David M.., Valentão, P.., & Andrade, P.. (2018). Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety. International Journal of Molecular Sciences , 19 . http://doi.org/10.3390/ijms19061668
20) Nørskov-Lauritsen, N.. (2014). Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans. Clinical Microbiology Reviews , 27 , 214 – 240 . http://doi.org/10.1128/CMR.00103-13
21) Pilli, R.., Rosso, G.., & Oliveira, M. C. D. de. (2010). The chemistry of Stemona alkaloids: An update.. Natural product reports , 27 12 , 1908-37 . http://doi.org/10.1039/c005018k
22) Radulović, N.., Blagojević, P.., Stojanović-Radić, Z.., & Stojanović, N.. (2013). Antimicrobial plant metabolites: structural diversity and mechanism of action.. Current medicinal chemistry , 20 7 , 932-52 . http://doi.org/10.2174/0929867311320070008
23) Radwan, M.., Chandra, S.., Gul, Shahbaz W.., & Elsohly, M.. (2021). Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis. Molecules , 26 . http://doi.org/10.3390/molecules26092774
24) Sellami, M.., Slimeni, O.., Pokrywka, A.., Kuvačić, Goran., Hayes, Lawrence D., Milić, M.., & Padulo, J.. (2018). Herbal medicine for sports: a review. Journal of the International Society of Sports Nutrition , 15 . http://doi.org/10.1186/s12970-018-0218-y
25) Singla, Rajeev K.., Dubey, A.., Garg, A.., Sharma, Ramesh K.., Fiorino, M.., Ameen, S. M.., Haddad, M.., & Al-Hiary, Masnat. (2019). Natural Polyphenols: Chemical Classification, Definition of Classes, Subcategories, and Structures.. Journal of AOAC International . http://doi.org/10.5740/jaoacint.19-0133
26) Steinestel, K.., Eder, S.., Schrader, A.., & Steinestel, J.. (2014). Clinical significance of epithelial-mesenchymal transition. Clinical and Translational Medicine , 3 , 17 – 17 . http://doi.org/10.1186/2001-1326-3-17
27) Tahtouh, Tania., Elkins, J.., Filippakopoulos, P.., Soundararajan, Meera., Burgy, Guillaume., Durieu, Emilie., Cochet, C.., Schmid, Ralf S.., Lo, D.., Delhommel, F.., Oberholzer, A.., Pearl, L.., Carreaux, F.., Bazureau, J.., Knapp, S.., & Meijer, L.. (2012). Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.. Journal of medicinal chemistry , 55 21 , 9312-30 . http://doi.org/10.1021/jm301034u
28) Wallwey, Christiane., & Li, Shu‐Ming. (2011). Ergot alkaloids: structure diversity, biosynthetic gene clusters and functional proof of biosynthetic genes.. Natural product reports , 28 3 , 496-510 . http://doi.org/10.1039/c0np00060d
29) Wang, Jin., Wang, Lin., Lou, Guanhua., Zeng, Hai-rong., Hu, Ju., Huang, Qin-wan., Peng, W.., & Yang, Xiang-bo. (2019). Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Pharmaceutical Biology , 57 , 193 – 225 . http://doi.org/10.1080/13880209.2019.1577466
30) Yan, Yumei., Li, Xing., Zhang, Chunhong., Lv, Li-juan., Gao, Bing., & Li, Minhui. (2021). Research Progress on Antibacterial Activities and Mechanisms of Natural Alkaloids: A Review. Antibiotics , 10 . http://doi.org/10.3390/antibiotics10030318
31) Zhang, Mengmeng., Wang, Jiaolong., Zhu, Lei., Li, Tao., Jiang, Weidong., Zhou, Juan., Peng, W.., & Wu, Chunjie. (2017). Zanthoxylum bungeanum Maxim. (Rutaceae): A Systematic Review of Its Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicology. International Journal of Molecular Sciences , 18 . http://doi.org/10.3390/ijms18102172
32) Zheng, Yi-Jun., Ren, W.., Zhang, Lina., Zhang, Yuemei., Liu, Dongling., & Liu, Yongqi. (2020). A Review of the Pharmacological Action of Astragalus Polysaccharide. Frontiers in Pharmacology , 11 . http://doi.org/10.3389/fphar.2020.00349