Immunization crisis may develop due to economic crisis during COVID-19 pandemic

COVID-19 pandemic is a global health crisis with 61, 149,391 confirmed cases and 370,478 deaths till 29May, 2020 [1]. This pandemic has shattered many economies with an estimated loss of $5.8 trillion to $8.8 trillion globally. This economic loss can result in reduction in funds to World Health Organization. Unfortunately, United States of America (USA) has announced termination of any further funding to WHO which can lead to another global health crisis[2]. As WHO is a voluntary funding based organization its main donor are America, China, Japan, Germany and United Kingdom. Among these USA is the main donor with a contribution of $115.8million alone followed by China $57.4 million, Japan $41million, Germany $29.1 million and UK $21.9 million [3].  America’s termination of funding can put WHO and child health programs in serious crisis. Among many programs run by WHO one of the most important program is immunization of children. Immunization coverage programs  save 2-3 million livesper year causing decline in measles related deaths, eradication of polio, surveillance of rotavirus, BCG and DTaP vaccination in children[4]. It is estimated that during MillenniumDevelopment Goal (MDG) there is overall decline in child related mortalities due to malaria, measles, diarrhea, AIDS and meningitis [5]. Remarkable results are achieved with measles are diarrhea immunization programs causing a decline in death rate by 73% and 80% respectively. According to a study with current success rate diarrhea related deaths can be virtually eliminated by 2030. Another successful program is “End Polio” program which eradicated polio from world except from Pakistan and Afghanistan [4][6]. This termination of funds to WHO can waste all previous efforts in developing countries. On the other hand despite of all efforts still 19.4 million children did not received prescribed dose of vaccines. Data analysis revealed among these  60% of children belong to 10 developing countries namelyAngola, Brazil, the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, Pakistan, the Philippines and Viet Nam [4]. These countries mainly rely on foreign funding and Non-Government Organization (NGOs) for child health care programs.

Phytochemical Studies of Lantana Camara Linn and Sturcture-Activity

The work embodied in the present thesis consists of two parts. Part A deals with the phytochemical studies on Lantana camara Linn., while part B describes the structure-activity relationship studies on some β-carboline alkaloids. A brief review of the biosynthesis of terpenoids with particular reference to the pentacyclic triterpenoids is also provided. PART A The introduction of Part A affords a review of the earlier contributions made in the chemistry and pharmacology of the genus Lantana and a brief account of the present work. Studies undertaken on the methanolic extract of the air dried aerial parts and roots of Lantana camara Linn. led to the isolation and structure elucidation of twenty four compounds including four new (17, 18, 21 and 23) and twenty known (1-16, 19, 20, 22 and 24) natural products. Compound 11 is hitherto unreported from aerial parts of the plant whereas compounds (4, 9 and 19) are reported for the first time from the genus Lantana. The constituents obtained in the present studies are listed below: Compounds obtained from aerial parts New Compounds 1. Lantanolide (17) 2. Lancamarolide (18) 3. Lancamarinic acid (21) 4. Lancamarinin (23) Known Compounds 5. Oleanonic acid (1) 6. b-Sitosterol (2) 7. Lantadene A (3) 8. 3-Oxo-11α-hydroxy-urs-12-ene-28-oic acid (4) 9. Oleanolic acid (5) 10. Ursolic acid (6) 11. Ursonic acid (7) 12. Betulinic acid (8) 13. 3β-Acetoxy Betulinic acid (9) 14. Lantadene B (10) 15. Pomonic acid (11) 16. Lantanilic acid (12) 17. Camaric acid (13) 18. Camarinic acid (14) 19. Lantaninilic acid (15) 20. Lantoic acid (16) 21. Stigmasterol (19) 22. Lantanolic acid (20) 23. Lantic acid (22) 24. β-Sitosterol-3-O-β-D-glucopyranoside (24) Compounds obtained from roots 1. Oleanonic acid (1) 2. Oleanolic acid (5) 3. Lantanilic acid (12) 4. β-Sitosterol-3-O-β-D-glucopyranoside (24) In the present investigation, the crude methanolic extract of the aerial parts of Lantana camara, its fractions and some pure compounds were evaluated for antileishmanial, nematicidal, mosquito larvicidal, anticancer and antioxidant activities. In addition, the extract and fractions were also evaluated for mosquito repellent, antibacterial, antifungal and insecticidal activities. Some pure compounds were also tested for immunomodulatory and enzyme inhibition activities. PART B The introduction of part B provides a review of the earlier contributions made in the chemistry and pharmacology of the β-carboline alkaloids – the harmine series of alkaloids. This part of the dissertation deals with the structure - activity relationship studies in the β-carboline alkaloids harmine (1), harmol (2) and harmalol (3) leading to the synthesis of thirty six derivatives (4-39) including eight new β-carbolines (20-25, 33 and 34) and five new tryptamine (35-39) derivatives along with several known compounds. Compounds 1 and 4-6 were tested for their leishmanicidal activity. Nematicidal activity of 2, 7, 8, 14-17 and 20-25 have also been determined. In addition compounds 2, 3 and 26-39 were tested for their antibacterial and antifungal activities. Some compounds were also investigated for their anticancer, chymotrypsin and urease inhibitory activities. The compounds synthesized in the present study are listed below: 1. 10-Bromo-11-methoxy-3-methyl-b-carboline (4) 2. 12-Bromo-11-methoxy-3-methyl-b-carboline (5) 3. 10,12-Dibromo-11-methoxy-3-methyl-b-carboline (6) 4. 10-Bromo-11-hydroxy-3-methyl-b-carboline (7) 5. 12-Bromo-11-hydroxy-3-methyl-b-carboline (8) 4 6. 11-Ethoxy-3-methyl-b-carboline (9) 7. 11-Butoxy-3-methyl-b-carboline (10) 8. 11-Isobutoxy-3-methyl-b-carboline (11) 9. 11-Pentoxy-3-methyl-b-carboline (12) 10. 11-Hexoxy-3-methyl-b-carboline (13) 11. 11-Heptoxy-3-methyl-b-carboline (14) 12. 11-Octoxy-3-methyl-b-carboline (15) 13. 11-Nonoxy-3-methyl-b-carboline (16) 14. 11-Decoxy-3-methyl-b-carboline (17) 15. 11-Allyloxy-3-methyl-b-carboline (18) 16. 11-Benzyloxy-3-methyl-b-carboline (19) 17. 11-2-Iodobenzyloxy-3-methyl-b-carboline (20) 18. 11-3-Iodobenzyloxy-3-methyl-b-carboline (21) 19. 11-4-Iodobenzyloxy-3-methyl-b-carboline (22) 20. 11-2-Nitrobenzyloxy-3-methyl-b-carboline (23) 21. 11-3-Nitrobenzyloxy-3-methyl-b-carboline (24) 22. 11-4-Nitrobenzyloxy-3-methyl-b-carboline (25) 23. 11-Acetoxy-3-methyl-b-carboline (26) 24. 11-Propionyloxy-3-methyl-b-carboline (27) 25. 11-Butyryloxy-3-methyl-b-carboline (28) 26. 11-Valeryloxy-3-methyl-b-carboline (29) 27. 11-Hexanoyloxy-3-methyl-b-carboline (30) 28. 11-Heptanoyloxy-3-methyl-b-carboline (31) 29. 11-Octanoyloxy-3-methyl-b-carboline (32) 5 30. 11-Nanoyloxy-3-methyl-b-carboline (33) 31. 11-Decanoyloxy-3-methyl-b-carboline (34) 32. 2-Acetyl-3-(2-nonanoylamidoethyl)-7-nonanoyloxyindole (35) 33. 2-Acetyl-3-(2-decanoylamidoethyl)-7-decanoyloxyindole (36) 34. 2-Acetyl-3-(2-trichloroacetamidoethyl)-7-trichloroacetoxyindole (37) 35. 2-Acetyl-3-[2-(2-trifloromethylbenzoyl)-amidoethyl]-7-(2- trifloromethyl benzoyloxy)-indole (38) 36. 2-Acetyl-3-[2-(3-trifloromethylbenzoyl)-amidoethyl)-7-(3- trifloromethyl benzoyloxy)-indole (39) Nematicidal activity was determined by Prof. Dr. Shaheena Fayyaz (Director) of the Institute of Nematological Research Center and Prof. Dr. Aly Khan (Director) of the Crop Disease Research Institute, Pakistan Agricultural Research Council, University of Karachi. Antimicrobial, antioxidant and immunomodulatory activities were tested by Prof. Dr. Aqeel Ahmed, Department of Microbiology, University of Karachi. Mosquito larvicidal and repellent activities were evaluated by Dr. M. Tariq Rajput, MAHQ Biological Research Centre, University of Karachi. Antileishmanial, anticancer, insecticidal and enzyme inhibition activities were determined by the bioassay screening section staff of this institute under the guidance of Prof. Dr. Muhammad Iqbal Choudhary. Extensive spectroscopic techniques such as UV, IR, EI-MS, HREI-MS, 1H- and 13C- NMR (Broad Band decoupled and DEPT), 2D NMR (1H-, 1H- COSY, NOESY, TOCSY, J-resolved, HMQC and HMBC) and chemical reactions were employed to elucidate the structures of the new compounds. The work embodied in the present dissertation has resulted in five research publications as listed in the list of publications.