Neglected Tropical Diseases: Current Treatment Challenges  and Future Therapeutic Potentials

Elhassan Hussein Eltom; Bandar Theyab Alenezi; Mohamed Soliman; Muhammad  Jan; Amro Soliman

doi:10.56782/pps.295

Published : 2025-04-05

Vol. 23 No. 2 (2025)

Neglected Tropical Diseases: Current Treatment Challenges and Future Therapeutic Potentials

Elhassan Hussein Eltom

Bandar Theyab Alenezi

Mohamed Soliman

Muhammad Jan

Amro Soliman

DOI: https://doi.org/10.56782/pps.295

Abstract

Neglected tropical diseases (NTDs) predominantly affect developing countries. Human African trypanosomiasis, leishmaniasis, Chagas disease, and malaria are protozoan infections that are endemic in developing countries and for which new drugs are desperately needed. Gaining better control of these diseases requires discovering and developing safe, effective, and affordable new drugs for the populations at risk. Unfortunately, incentives for the research and development of new medicine to combat NTDs are currently insufficient. This paper examines recent efforts to increase R&D investments in the development of new anti-parasitic drugs and provides an overview of the most recent and promising compounds at different development stages for each pathogen. Additionally, information on the development of novel formulations combining existing drugs and delivery systems that can improve therapeutic outcomes as well as recent advances in drug discovery, obstacles to developing new chemical entities (NCEs), and the role of public-private partnerships (PPPs) are discussed. In conclusion, drug discovery for neglected diseases entails a larger challenge of demonstrating translational readiness at an early stage. Classification systems can help identify gaps and focus research and development efforts on candidates with the highest likelihood of becoming clinical options. To overcome funding shortages and reduce the incubation time for promising drug discovery initiatives, it is necessary to harness the power of collaborative networks and use innovative funding models.

Keywords:

Neglected tropical diseases, anti-parasitic drugs, protozoan infections, innovative funding models

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Eltom, E. H., Alenezi, B. T., Soliman, M., Jan, M., & Soliman, A. (2025). Neglected Tropical Diseases: Current Treatment Challenges and Future Therapeutic Potentials. Prospects in Pharmaceutical Sciences, 23(2), 1–9. https://doi.org/10.56782/pps.295

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References

1. Simon, G. G. Impacts of Neglected Tropical Disease on Incidence and Progression of HIV/AIDS, Tuberculosis, and Malaria: Scientific Links. Int. J. Inf. Dis. 2016, 42,54–57. DOI: 10.1016/j.ijid.2015.11.006

2. Kourbeli, V.; Chontzopoulou, E.; Moschovou, K.; Pavlos, D.; Mavromoustakos, T.; Papanastasiou, I. P. An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases. Molecules 2021, 26 (15), Art. No: 4629. DOI: 10.3390/molecules26154629

3. Mukherjee, S. The United States Food and Drug Administration (FDA) Regulatory Response to Combat Neglected Tropical Diseases (NTDs): A Review. PLoS Negl. Trop. Dis. 2023, 17 (1), Art. No: e0011010. DOI: 10.1371/journal.pntd.0011010

4. Lin, Y.; Fang, K.; Zheng, Y.; Wang, H.; Wu, J. Global Burden and Trends of Neglected Tropical Diseases from 1990 to 2019. J. Travel Med. 2022, 29 (3), Art. No: taac031. DOI: 10.1093/jtm/taac031

5. Ca, J.; Kumar P, V. B.; Kandi, V.; N, G.; K, S.; Dharshini, D.; Batchu, S. V. C.; Bhanu, P. Neglected Tropical Diseases: A Comprehensive Review. Cureus. 2024,16(2), Art. No: e53933 DOI: 10.7759/cureus.53933

6. Pandian, S. R. K.; Panneerselvam, T.; Pavadai, P.; Govindaraj, S.; Ravishankar, V.; Palanisamy, P.; Sampath, M.; Sankaranarayanan, M.; Kunjiappan, S. Nano Based Approach for the Treatment of Neglected Tropical Diseases. Front. Nanotechnol. 2021, 3, Art. No: 665274. DOI: 10.3389/fnano.2021.665274

7. Ayon, N. J. High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery. Metabolites 2023, 13 (5), Art. No: 625. DOI: 10.3390/metabo13050625

8. Blay, V.; Tolani, B.; Ho, S. P.; Arkin, M. R. High-Throughput Screening: Today’s Biochemical and Cell-Based Approaches. Drug Dis. Today 2020, 25 (10), 1807–1821. DOI: 10.1016/j.drudis.2020.07.024

9. Vatansever, S.; Schlessinger, A.; Wacker, D.; Kaniskan, H. Ü.; Jin, J.; Zhou, M.; Zhang, B. Artificial Intelligence and Machine Learning‐aided Drug Discovery in Central Nervous System Diseases: State‐of‐the‐arts and Future Directions. Med. Res. Rev. 2021, 41 (3), 1427–1473. DOI: 10.1002/med.21764

10. Makhoba, X. H.; Viegas, C.; Mosa, R. A.; Viegas, F. P. D.; Pooe, O. J. Potential Impact of the Multi-Target Drug Approach in the Treatment of Some Complex Diseases. Drug Des. Devel. Ther. 2020, 14, 3235–3249. DOI: 10.2147/DDDT.S257494

11. Gao, K.; Shaabani, S.; Xu, R.; Zarganes-Tzitzikas, T.; Gao, L.; Ahmadianmoghaddam, M.; Groves, M. R.; Dömling, A. Nanoscale, Automated, High Throughput Synthesis and Screening for the Accelerated Discovery of Protein Modifiers. RSC Med. Chem. 2021, 12 (5), 809–818. DOI: 10.1039/D1MD00087J

12. Quarleri, J.; Cevallos, C.; Delpino, M. V. Apoptosis in Infectious Diseases as a Mechanism of Immune Evasion and Survival. In Advances in Protein Chemistry and Structural Biology; Elsevier, 2021; Vol. 125, pp 1–24. DOI: 10.1016/bs.apcsb.2021.01.001

13. Pillaiyar, T.; Meenakshisundaram, S.; Manickam, M.; Sankaranarayanan, M. A Medicinal Chemistry Perspective of Drug Repositioning: Recent Advances and Challenges in Drug Discovery. Eur. J. Med. Chem. 2020, 195, Art. No: 112275. DOI: 10.1016/j.ejmech.2020.112275

14. Debbarma, S.; Talukdar, J.; Maurya, P.; Barkalita, L. M.; Brahma, A. Neglected Parasitic Infections: History to Current Status. In Parasitic Infections; Mishra, A. P., Nigam, M., Eds.; Wiley, 2023; pp 156–175. DOI: 10.1002/9781119878063.ch8

15. Profiro De Oliveira, J. H.; Arruda, I. E. S.; Izak Ribeiro De Araújo, J.; Chaves, L. L.; De La Rocca Soares, M. F.; Soares-Sobrinho, J. L. Why Do Few Drug Delivery Systems to Combat Neglected Tropical Diseases Reach the Market? An Analysis from the Technology’s Stages. Expert Opin. Ther. Pat. 2022, 32 (1), 89–114. DOI: 10.1080/13543776.2021.1970746

16. Borgo, J.; Laurella, L. C.; Nápoles Rodríguez, R.; De Almeida Fiuza, L.; Sülsen, V. P. The Potential Use of Natural Products as Sources of Bioactive Compounds: Searching for New Treatments for Neglected Tropical Diseases. In Studies in Natural Products Chemistry; Elsevier, 2024; Vol. 81, pp 133–212. DOI: 10.1016/B978-0-443-15628-1.00018-0

17. Jayawardene, K. L. T. D.; Palombo, E. A.; Boag, P. R. Natural Products Are a Promising Source for Anthelmintic Drug Discovery. Biomolecules 2021, 11 (10), Art. No: 1457. DOI: 10.3390/biom11101457.

18. Ndjonka, D.; Rapado, L. N.; Silber, A. M.; Liebau, E.; Wrenger, C. Natural Products as a Source for Treating Neglected Parasitic Diseases. Int. J. Mol. Sci. 2013, 14 (2), 3395–3439. DOI: 10.3390/ijms14023395

19. Carter, N. S.; Stamper, B. D.; Elbarbry, F.; Nguyen, V.; Lopez, S.; Kawasaki, Y.; Poormohamadian, R.; Roberts, S. C. Natural Products That Target the Arginase in Leishmania Parasites Hold Therapeutic Promise. Microorganisms 2021, 9 (2), Art. No: 267. DOI: 10.3390/microorganisms9020267

20. Liu, M.; Panda, S. K.; Luyten, W. Plant-Based Natural Products for the Discovery and Development of Novel Anthelmintics against Nematodes. Biomolecules 2020, 10 (3), Art. No: 426. DOI: 10.3390/biom10030426

21. Mustapha, T.; Daskum, A.; Chessed, G.; A. Qadeer, M. Antimarial Chemotherapy, Mechanism of Action and Resistance to Major Antimalarial Drugs in Clinical Use: A Review. Microbes Infect. Dis. 2021, 2(1), 130-142. DOI: 10.21608/mid.2020.43941.1064

22. Darko, B. A.; Owusu-Asenso, C. M.; Mensah, A.; Seyram, A. C.; Dzotefe, G.B.; Ebobabaara, T.B.; Opoku-Gyebi, F.; Gordor, B.Y.; Obeng, B.C. Global Trends in the Burden of Malaria: Contemporary Diagnostic Approaches, and Treatment Strategies. World J. Adv. Res. Rev. 2023, 20 (1), 258–272. DOI: 10.30574/wjarr.2023.20.1.2038

23. The Lancet Infectious Diseases. A New Dawn for Malaria Prevention. Lancet Infect. Dis. 2024, 24 (2), Art. No: 107. DOI: 10.1016/S1473-3099(24)00012-4

24. Shi, D.; Wei, L.; Liang, H.; Yan, D.; Zhang, J.; Wang, Z. Trends of the Global, Regional and National Incidence, Mortality, and Disability-Adjusted Life Years of Malaria, 1990–2019: An Analysis of the Global Burden of Disease Study 2019. Risk Manag. Healthc. Policy 2023, 16, 1187–1201. DOI: 10.2147/RMHP.S419616

25. Aschale, Y.; Getachew, A.; Yewhalaw, D.; De Cristofaro, A.; Sciarretta, A.; Atenafu, G. Systematic Review of Sporozoite Infection Rate of Anopheles Mosquitoes in Ethiopia, 2001–2021. Parasit. Vectors 2023, 16 (1), Art. No: 437. DOI: 10.1186/s13071-023-06054-y

26. Tang, Y.-Q.; Ye, Q.; Huang, H.; Zheng, W.-Y. An Overview of Available Antimalarials: Discovery, Mode of Action and Drug Resistance. Curr. Mol. Med. 2020, 20 (8), 583–592. DOI: 10.2174/1566524020666200207123253

27. Voorberg-van Der Wel, A.; Kocken, C. H. M.; Zeeman, A.-M. Modeling Relapsing Malaria: Emerging Technologies to Study Parasite-Host Interactions in the Liver. Front. Cell. Infect. Microbiol. 2021, 10, Art. No: 606033. DOI: 10.3389/fcimb.2020.606033

28. Turner, T.C., Arama, C., Ongoiba, A., Doumbo, S., Doumtabé, D., Kayentao, K., Skinner, J., Li, S., Traore, B., Crompton, P.D., Götz, A. Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting. Malar. J. 2021, 20(1), Art. No: 9. DOI: 10.1186/s12936-020-03533-w

29. Yadav, G. P.; Arukha, A. P.; Kothapalli, Y.; Singh, U. S. Antimalarial Drugs: Discovery, Mechanism of Action, and Drug Resistance. In Falciparum Malaria; Elsevier, 2024; pp 89–112. DOI: 10.1016/B978-0-323-95328-3.00008-8

30. Shandilya, C.; Singh, S.; Bala, K.; Singh, A.; Jha, S. K.; Singh, I. K. Malaria Drug Discovery: How to Tackle the Problem of Drug Resistance. In Natural Product Based Drug Discovery Against Human Parasites; Singh, A., Rathi, B., Verma, A. K., Singh, I. K., Eds.; Springer Nature Singapore: Singapore, 2023; pp 491–510. DOI: 10.1007/978-981-19-9605-4_22

31. Kofi Turkson, B.; Ofori Agyemang, A.; Nkrumah, D.; Isaac Nketia, R.; Frimpong Baidoo, M.; Lincoln Kwao Mensah, M. Treatment of Malaria Infection and Drug Resistance. In Plasmodium Species and Drug Resistance; K. Tyagi, R., Ed.; IntechOpen, 2021. DOI: 10.5772/intechopen.98373

32. López-Vélez, R.; Norman, F. F.; Bern, C. American Trypanosomiasis (Chagas Disease). In Hunter’s Tropical Medicine and Emerging Infectious Diseases; Elsevier, 2020; pp 762–775. DOI: 10.1016/B978-0-323-55512-8.00103-4

33. Malone, C. J.; Nevis, I.; Fernández, E.; Sanchez, A. A Rapid Review on the Efficacy and Safety of Pharmacological Treatments for Chagas Disease. Trop. Med. Infect. Dis. 2021, 6 (3), Art. No: 128. DOI: 10.3390/tropicalmed6030128

34. Ramos, L. G.; De Souza, K. R.; Júnior, P. A. S.; Câmara, C. C.; Castelo-Branco, F. S.; Boechat, N.; Carvalho, S. A. Tackling the Challenges of Human Chagas Disease: A Comprehensive Review of Treatment Strategies in the Chronic Phase and Emerging Therapeutic Approaches. Acta Trop. 2024, 256, Art. No: 107264. DOI: 10.1016/j.actatropica.2024.107264

35. Álvarez-Hernández, D.-A.; Castro-Rico, Z.-L.; García-Rodríguez-Arana, R.; González-Chávez, A.-M.; González-Chávez, M.-A.; Martínez-Juárez, L.-A.; Ferreira, C.; Vázquez-López, R. Current Treatment of Chagas Disease. Curr. Treat. Options Infect. Dis. 2020, 12 (4), 438–457. DOI: 10.1007/s40506-020-00238-1

36. Chaudhary, J.; Rajge, R. R.; Khandale, N.; Kumari, Y.; Singh, I. Alternative Approaches for the Treatment of Chagas Disease. ChemistrySelect. 2024, 9 (18), Art. No: e202303983. DOI: 10.1002/slct.202303983

37. Nunes, M. C. P.; Bern, C.; Clark, E. H.; Teixeira, A. L.; Molina, I. Clinical Features of Chagas Disease Progression and Severity. Lancet Reg. Health Am. 2024, 37, Art. No: 100832. DOI: 10.1016/j.lana.2024.100832

38. Sabino, E. C.; Nunes, M. C. P.; Blum, J.; Molina, I.; Ribeiro, A. L. P. Cardiac Involvement in Chagas Disease and African Trypanosomiasis. Nat. Rev. Cardiol. 2024, 21 (12), 865–879. DOI: 10.1038/s41569-024-01057-3

39. Goldenberg, S. Chagas Disease Treatment: A 120-Year-Old Challenge to Public Health. Mem. Inst. Oswaldo Cruz. 2022, 117, Art. No: e210501chgsa. DOI: 10.1590/0074-02760210501chgsa

40. Suárez, C.; Nolder, D.; García-Mingo, A.; Moore, D. A.; Chiodini, P. L. Diagnosis and Clinical Management of Chagas Disease: An Increasing Challenge in Non-Endemic Areas. Res. Rep. Trop. Med. 2022, 13, 25–40. DOI: 10.2147/RRTM.S278135

41. Tripathi, L. K.; Nailwal, T. K. Leishmaniasis: An Overview of Evolution, Classification, Distribution, and Historical Aspects of Parasite and Its Vector. In Pathogenesis, Treatment and Prevention of Leishmaniasis; Elsevier, 2021; pp 1–25. DOI: 10.1016/B978-0-12-822800-5.00004-4

42. Saini, I.; Joshi, J.; Kaur, S. Unwelcome Prevalence of Leishmaniasis with Several Other Infectious Diseases. Int. Immunopharmacol. 2022, 110, Art. No: 109059. DOI: 10.1016/j.intimp.2022.109059

43. Mohan, S.; Revill, P.; Malvolti, S.; Malhame, M.; Sculpher, M.; Kaye, P. M. Estimating the Global Demand Curve for a Leishmaniasis Vaccine: A Generalisable Approach Based on Global Burden of Disease Estimates. PLoS Negl. Trop. Dis. 2022, 16 (6), Art. No: e0010471. DOI: 10.1371/journal.pntd.0010471

44. Wijnant, G.-J.; Dumetz, F.; Dirkx, L.; Bulté, D.; Cuypers, B.; Van Bocxlaer, K.; Hendrickx, S. Tackling Drug Resistance and Other Causes of Treatment Failure in Leishmaniasis. Front. Trop. Dis. 2022, 3, Art. No: 837460. DOI: 10.3389/fitd.2022.837460

45. Sundar, S.; Singh, J.; Singh, V. K.; Agrawal, N.; Kumar, R. Current and Emerging Therapies for the Treatment of Leishmaniasis. Expert Opin. Orphan Drugs 2024, 12 (1), 19–32. DOI: 10.1080/21678707.2024.2335248

46. Jain, S.; Sahu, U.; Kumar, A.; Khare, P. Metabolic Pathways of Leishmania Parasite: Source of Pertinent Drug Targets and Potent Drug Candidates. Pharmaceutics 2022, 14 (8), 1590. DOI: 10.3390/pharmaceutics14081590

47. Kourbeli, V.; Chontzopoulou, E.; Moschovou, K.; Pavlos, D.; Mavromoustakos, T.; Papanastasiou, I. P. An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases. Molecules 2021, 26 (15), Art. No: 4629. DOI: 10.3390/molecules26154629

48. Rout, U. K.; Sanket, A. S.; Sisodia, B. S.; Mohapatra, P. K.; Pati, S.; Kant, R.; Dwivedi, G. R. A Comparative Review on Current and Future Drug Targets Against Bacteria & Malaria. Curr. Drug Targets 2020, 21 (8), 736–775. DOI: 10.2174/1389450121666200129103618

49. Chulanetra, M.; Chaicumpa, W. Revisiting the Mechanisms of Immune Evasion Employed by Human Parasites. Front. Cell. Infect. Microbiol. 2021, 11, Art. No: 702125. DOI: 10.3389/fcimb.2021.702125

50. Gabaldón-Figueira, J. C.; Martinez-Peinado, N.; Escabia, E.; Ros-Lucas, A.; Chatelain, E.; Scandale, I.; Gascon, J.; Pinazo, M.-J.; Alonso-Padilla, J. State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation. Res. Rep. Trop. Med. 2023, 14, 1–19. DOI: 10.2147/RRTM.S415273

51. Gilbert, I.H. Drug discovery for neglected diseases: molecular target-based and phenotypic approaches. J. Med. Chem. 2013, 56(20), 7719-26. DOI: 10.1021/jm400362b

52. Belmont-Díaz, J.; Vázquez, C.; Encalada, R.; Moreno-Sánchez, R.; Michels, P. A. M.; Saavedra, E. Metabolic Control Analysis for Drug Target Selection Against Human Diseases. In Drug Target Selection and Validation; Scotti, M. T., Bellera, C. L., Eds.; Book Series: Computer-Aided Drug Discovery and Design; Springer International Publishing: Cham, 2022; Vol. 1, pp 201–226. DOI: 10.1007/978-3-030-95895-4_8

53. Parthasarathy, A.; Kalesh, K. Defeating the Trypanosomatid Trio: Proteomics of the Protozoan Parasites Causing Neglected Tropical Diseases. RSC Med. Chem. 2020, 11 (6), 625–645. DOI: 10.1039/D0MD00122H

54. Koul, S. Divergent Approaches Toward Drug Discovery and Development. In The Quintessence of Basic and Clinical Research and Scientific Publishing; Jagadeesh, G., Balakumar, P., Senatore, F., Eds.; Springer Nature Singapore: Singapore, 2023; pp 557–578. DOI: 10.1007/978-981-99-1284-1_34

55. Pant, A. M.; Pelham, C. J.; Jadhav, G. P. Epigenetic Drug Discovery: Recent Advances through Structure-Activity Relationships and Phenotypic Profiling Studies. In Epigenetics in Organ Specific Disorders; Elsevier, 2023; pp 615–630. DOI: 10.1016/B978-0-12-823931-5.00009-8

56. Kotadiya, M. Drug Repurposing: Scopes in Herbal/Natural Products-Based Drug Discovery and Role of in Silico Techniques. In Drug Repurposing - Advances, Scopes and Opportunities in Drug Discovery; Rudrapal, M., Ed.; IntechOpen, 2023. DOI: 10.5772/intechopen.109821.

57. Shaivi, L.; Turabi, K. S.; Aich, J.; Devarajan, S.; Unni, D.; Garse, S. In Silico Approaches in the Repurposing of Bioactive Natural Products for Drug Discovery. In Phytochemistry, Computational Tools and Databases in Drug Discovery; Elsevier, 2023; pp 125–147. DOI: 10.1016/B978-0-323-90593-0.00010-1

58. Camicia, F.; Vaca, H. R.; Park, S.-K.; Bivona, A. E.; Naidich, A.; Preza, M.; Koziol, U.; Celentano, A. M.; Marchant, J. S.; Rosenzvit, M. C. Characterization of a New Type of Neuronal 5-HT G- Protein Coupled Receptor in the Cestode Nervous System. PLoS ONE 2021, 16 (11), Art. No: e0259104. DOI: 10.1371/journal.pone.0259104

59. Montazeri, M.; Fakhar, M.; Keighobadi, M. The Potential Role of the Serotonin Transporter as a Drug Targetagainst Parasitic Infections: A Scoping Review of the Literature. Recent Adv .Antiinfect. Drug Discov. 2022, 17 (1), 23–33. DOI: 10.2174/1574891X16666220304232301

60. Sutkeviciute, I.; Vilardaga, J.-P. Structural Insights into Emergent Signaling Modes of G Protein–Coupled Receptors. J. Biol. Chem. 2020, 295 (33), 11626–11642. DOI: 10.1074/jbc.REV120.009348

61. Kumar, A.; Deepika; Sharda, S.; Avasthi, A. Recent Advances in the Treatment of Parasitic Diseases: Current Status and Future. In Natural Product Based Drug Discovery Against Human Parasites; Singh, A., Rathi, B., Verma, A. K., Singh, I. K., Eds.; Springer Nature Singapore: Singapore, 2023; pp 249–286. DOI: 10.1007/978-981-19-9605-4_13

62. J. Timson, D. Metabolic Enzymes of Helminth Parasites: Potential as Drug Targets. Curr. Protein Pept. Sci. 2016, 17 (3), 280–295. DOI: 10.2174/1389203717999160226180733

63. Lautens, M. J.; Tan, J. H.; Serrat, X.; Del Borrello, S.; Schertzberg, M. R.; Fraser, A. G. Identification of Enzymes That Have Helminth-Specific Active Sites and Are Required for Rhodoquinone-Dependent Metabolism as Targets for New Anthelmintics. PLoS Negl. Trop. Dis. 2021, 15 (11), Art. No: e0009991. DOI: 10.1371/journal.pntd.0009991

64. Taylor, C. M.; Wang, Q.; Rosa, B. A.; Huang, S. C.-C.; Powell, K.; Schedl, T.; Pearce, E. J.; Abubucker, S.; Mitreva, M. Discovery of Anthelmintic Drug Targets and Drugs Using Chokepoints in Nematode Metabolic Pathways. PLoS Pathog. 2013, 9 (8), Art. No: e1003505. DOI: 10.1371/journal.ppat.1003505

65. Jampilek, J. Design of Antimalarial Agents Based on Natural Products. Curr. Org. Chem. 2017, 21 (18), 1824-1846. DOI: 10.2174/1385272821666161214121512

66. Ahad, B.; Shahri, W.; Rasool, H.; Reshi, Z. A.; Rasool, S.; Hussain, T. Medicinal Plants and Herbal Drugs: An Overview. In Medicinal and Aromatic Plants; Aftab, T., Hakeem, K. R., Eds.; Springer International Publishing: Cham., 2021; pp 1–40. DOI: 10.1007/978-3-030-58975-2_1

67. El Sayed, A. M.; Egbuna, C. Novel Bioactive Lead Compounds for Drug Discovery Against Neglected Tropical Diseases, Leishmaniasis, Lymphatic Filariasis, Trypanosomiasis (African Sleeping Sickness and Chagas Disease), and Schistosomiasis. In Neglected Tropical Diseases and Phytochemicals in Drug Discovery; Egbuna, C., Akram, M., Ifemeje, J. C., Eds.; Wiley, 2021; pp 75–134. DOI: 10.1002/9781119617143.ch3

68. Chithra, A.; Dhivya, K.; I., S. S.; Suresh, A. R.; Balasubramaniyan, M. Phytocompounds as Therapeutic Agents Against Neglected Tropical Diseases: In Advances in Medical Diagnosis, Treatment, and Care; Radhakrishnan, N., Vasantha, S., Pandurangan, A. K., Eds.; IGI Global, 2023; pp 200–224. DOI: 10.4018/978-1-6684-6737-4.ch012

69. Soto‐Sánchez, J. Could Natural Terpenes Be an Alternative for the Treatment of Neglected Tropical Diseases? Chem. Biol. Drug Des. 2024, 103 (2), Art. No: e14470. DOI: 10.1111/cbdd.14470

70. Adegboye, O.; Field, M. A.; Kupz, A.; Pai, S.; Sharma, D.; Smout, M. J.; Wangchuk, P.; Wong, Y.; Loiseau, C. Natural-Product-Based Solutions for Tropical Infectious Diseases. Clin. Microbiol. Rev. 2021, 34 (4), e00348-20. DOI: 10.1128/CMR.00348-20

71. Raj, S.; Sasidharan, S.; Balaji, S. N.; Dubey, V. K.; Saudagar, P. Review on Natural Products as an Alternative to Contemporary Anti-Leishmanial Therapeutics. J. Proteins Proteom. 2020, 11 (2), 135–158. DOI: 10.1007/s42485-020-00035-w

72. Abdullah; Khan, F.; Ali, G.; Naveed, A.; Shah, M. A.; Saleem, U.; Aman, W. Phytonutrients Standardization for Effective Therapeutic Outcomes. In Phytonutrients and Neurological Disorders; Elsevier, 2023; pp 19–31. DOI: 10.1016/B978-0-12-824467-8.00010-3

73. Barani, M.; Sangiovanni, E.; Angarano, M.; Rajizadeh, M. A.; Mehrabani, M.; Piazza, S.; Gangadharappa, H. V.; Pardakhty, A.; Mehrbani, M.; Dell’Agli, M.; et al. Phytosomes as Innovative Delivery Systems for Phytochemicals: A Comprehensive Review of Literature. Int. J. Nanomedicine 2021, 16, 6983–7022. DOI: 10.2147/IJN.S318416

74. Estrella-Parra, E. A.; Arreola, R.; Álvarez-Sánchez, M. E.; Torres-Romero, J. C.; Rojas-Espinosa, O.; De La Cruz-Santiago, J. A.; Martinez-Benitez, M. B.; López-Camarillo, C.; Lara-Riegos, J. C.; Arana-Argáez, V. E.; et al. Natural Marine Products as Antiprotozoal Agents against Amitochondrial Parasites. Int. J. Parasitol. Drugs Drug Resist. 2022, 19, 40–46. DOI: 10.1016/j.ijpddr.2022.05.003

75. Venkateskumar, K.; Parasuraman, S.; Chuen, L. Y.; Ravichandran, V.; Balamurgan, S. Exploring Antimicrobials from the Flora and Fauna of Marine: Opportunities and Limitations. Curr. Drug Discov. Technol. 2020, 17 (4), 507–514. DOI: 10.2174/1570163816666190819141344

76. Santhiravel, S.; Dave, D.; Shahidi, F. Bioactives from Marine Resources as Natural Health Products: A Review. Pharmacol. Rev. 2024, Art. No: PHARMREV-AR-2024-001227. DOI: 10.1124/pharmrev.124.001227

77. Banday, A. H.; Azha, N. U.; Farooq, R.; Sheikh, S. A.; Ganie, M. A.; Parray, M. N.; Mushtaq, H.; Hameed, I.; Lone, M. A. Exploring the Potential of Marine Natural Products in Drug Development: A Comprehensive Review. Phytochem. Lett. 2024, 59, 124–135. DOI: 10.1016/j.phytol.2024.01.001

78. Mendoza-Muñoz, N.; Urbán-Morlán, Z.; Leyva-Gómez, G.; Zambrano-Zaragoza, M. D. L. L.; ¨Piñón-Segundo, E.; Quintanar-Guerrero, D. Solid Lipid Nanoparticles: An Approach to Improve Oral Drug Delivery. J. Pharm. Pharm. Sci. 2021, 24, 509–532. DOI: 10.18433/jpps31788.

79. De Carvalho Oliveira, S. S.; Branquinha, M. H.; Do Socorro Pires E Cruz, M.; Santos, A. L. S. D.; Sangenito, L. S. Trendings of Amphotericin B-Loaded Nanoparticles as Valuable Chemotherapeutic Approaches against Leishmaniasis. In Applications of Nanobiotechnology for Neglected Tropical Diseases; Elsevier, 2021; pp 291–327. DOI: 10.1016/B978-0-12-821100-7.00014-5

80. Muraca, G.; Berti, I. R.; Sbaraglini, M. L.; Fávaro, W. J.; Durán, N.; Castro, G. R.; Talevi, A. Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers. Front. Chem. 2020, 8, Art. No: 601151. DOI: 10.3389/fchem.2020.601151

81. Ortega, M. Á.; Guzmán Merino, A.; Fraile-Martínez, O.; Recio-Ruiz, J.; Pekarek, L.; G. Guijarro, L.; García-Honduvilla, N.; Álvarez-Mon, M.; Buján, J.; García-Gallego, S. Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases. Pharmaceutics 2020, 12 (9), Art. No: 874. DOI: 10.3390/pharmaceutics12090874

82. Maddiboyina, B.; Ramaiah; Nakkala, R. K.; Roy, H. Perspectives on Cutting‐edge Nanoparticulate Drug Delivery Technologies Based on Lipids and Their Applications. Chem. Biol. Drug Des. 2023, 102 (2), 377–394. DOI: 10.1111/cbdd.14230.

83. Ahmed, T.; Liu, F.-C. F.; Wu, X. Y. An Update on Strategies for Optimizing Polymer-Lipid Hybrid Nanoparticle-Mediated Drug Delivery: Exploiting Transformability and Bioactivity of PLN and Harnessing Intracellular Lipid Transport Mechanism. Expert Opin. Drug Deliv. 2024, 21 (2), 245–278. DOI: 10.1080/17425247.2024.2318459

84. Pundir, G. .; Morris, S. .; Jakhmola, V.; Parashar, T. P. . Microneedle Transdermal Patches - A Novel Painless Approach with Improved Bioavailability for the Treatment of Diseases with Special Prevalence to Neonatal Infection. IJDDT 2024, 14 (03), 1749–1757. DOI: 10.25258/ijddt.14.3.71

85. Sekar, L.; Seenivasan, R.; Reddy, M. V.; Varma, K. D.; Ahmed, S. S.; Pachiyappan, J. K.; Ganesh, G. Advancements in microneedle technology: comprehensive insights into versatile drug delivery mechanisms. Int. J. App. Pharm. 2024, 16, 1–11. DOI: 10.22159/ijap.2024v16i2.49564.

86. Martin-Plaza, J.; Chatelain, E. Novel Therapeutic Approaches for Neglected Infectious Diseases. SLAS Dis. 2015, 20 (1), 3–5. DOI: 10.1177/1087057114559907

87. Aldawood, F. K.; Parupelli, S. K.; Andar, A.; Desai, S. 3D Printing of Biodegradable Polymeric Microneedles for Transdermal Drug Delivery Applications. Pharmaceutics 2024, 16 (2), Art. No: 237. DOI: 10.3390/pharmaceutics16020237

88. Mendoza-León, A.; Serrano G., M. L.; Ponte-Sucre, A. Challenges in Drug Discovery and Description Targeting Leishmania Spp.: Enzymes, Structural Proteins, and Transporters. Front. Trop. Dis. 2023, 4, Art. No: 1241044. DOI: 10.3389/fitd.2023.1241044.

89. Bello‐Akinosho, M.; Afolabi, K. O.; Chandra, H.; Mayashinta, D. K.; Setia, Y. D.; Prakash Mishra, A.; Pohl‐Albertyn, C. Opportunities and Challenges in the Development of Antiparasitic Drugs. In Parasitic Infections; Mishra, A. P., Nigam, M., Eds.; Wiley, 2023; pp 227–250. DOI: 10.1002/9781119878063.ch11

90. Schmidt, H.; Mauer, K.; Glaser, M.; Dezfuli, B. S.; Hellmann, S. L.; Silva Gomes, A. L.; Butter, F.; Wade, R. C.; Hankeln, T.; Herlyn, H. Identification of Antiparasitic Drug Targets Using a Multi-Omics Workflow in the Acanthocephalan Model. BMC Genomics. 2022, 23 (1), Art. No: 677. DOI: 10.1186/s12864-022-08882-1

91. Kiriiri, G. K.; Njogu, P. M.; Mwangi, A. N. Exploring Different Approaches to Improve the Success of Drug Discovery and Development Projects: A Review. Futur. J. Pharm. Sci. 2020, 6 (1), Art. No: 27. DOI: 10.1186/s43094-020-00047-9

92. Yajima, A., Lin, Z., Mohamed, A.J., Dash, A.P., Rijal, S. Finishing the task of eliminating neglected tropical diseases (NTDs) in WHO South-East Asia Region: promises kept, challenges, and the way forward. Lancet Reg. Health Southeast Asia. 2023, 18, Art. No: 100302. DOI: 10.1016/j.lansea.2023.100302

93. Ungogo, M. A.; Ebiloma, G. U.; Ichoron, N.; Igoli, J. O.; De Koning, H. P.; Balogun, E. O. A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora. Front. Chem. 2020, 8, Art. No: 617448. DOI: 10.3389/fchem.2020.617448

Elhassan Hussein Eltom

Affiliation:

Professor at the Department of Pharmacology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia. Saudi Arabia

Bandar Theyab Alenezi

Affiliation:

Professor at the Department of Pharmacology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia. Saudi Arabia

Mohamed Soliman

Affiliation:

Professor at the Department of Microbiology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia and the Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Saudi Arabia

Muhammad Jan

Affiliation:

Professor at the Department of Pharmacology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia Saudi Arabia

Amro Soliman

amro.soliman@concordia.ab.ca

Affiliation:

a:1:{s:5:"en_US";s:20:"Assistant Professor ";} Canada