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.

Syntheses of Pyridine and Pyrimidine Derivatives in Search of Potential Therapeutic Agents

This research work consists of the syntheses of pyridine and pyrimidine derivatives by adopting various synthetic chemical transformations and screening of their biological activities. All compounds were fully characterized by various spectroscopic techniques such as 1H-NMR, 13C-NMR, EI-MS and HREI-MS. Melting points of all compounds were also recorded. This dissertation consists of two chapters based on the extensive literature and research findings regarding the three libraries of synthetic compounds. Each chapter has its own compounds numbering, tables, figures, schemes and references. Chapter-1 has been subdivided into two parts (part A and B). Part A composed of the broad literature survey regarding the general introduction of pyridine, its biological background and various synthetic protocols. In addition, it also deals with the rationale behind the current study. Fifty-seven synthesized derivatives of pyridine (21-77) were evaluated for their in vitro activities. all derivatives showed more potent inhibition against α-glucosidase in vitro, however, compounds 29, 35, 43, 44, 49, 56, 61, 70, and 75 showed more than hundred-fold better activity than standard acarbose (IC50 = 856.45 ± 5.60 μM). Out of fifty-seven derivatives, only four compounds 28, 30, 42, and 43 showed weak in vitro dipeptidyl peptidase inhibitory activity as compared to standard sitagliptin (IC50 = 0.0246 ± 0.004 µM). Remaining compounds were found to be completely inactive. Compound 38 showed potent antileishmanial activity while compound 22, 39, 40, 41, 46, 49, 55, and 67 showed weak to significant antileishmanial activities when compared with the standards amphotericin B (IC50 = 0.29 ± 0.05 µM) and pentamidine (IC50 = 5.09 ± 0.04 µM). Ten analogs 22, 25, 35, 38, 42, 46, 49, 63, 70, and 75 manifested themselves to be more potent while ten anlogs 31, 33, 36, 37, 39, 41, 45, 57, 73, and 74 showed weak to moderate activity in comparison with standard ibuprofen (IC50 = 11.2 ± 1.9 µM). Four analogs 25, 28, 35, and 49 were attributed to be significantly active while 43 showed moderate activity in comparison with standard rutin. Only compound 64 was observed to be the most potent against tyrosinase enzyme while, derivative 21, 38, and 50 showed moderate to weak tyrosinase inhibitory activity. In Part-B further pyridine derivatives 78-118 were synthesized and screened to check their in vitro biological activities. In vitro β-glucuronidase inhibition of all synthetic derivatives 78-118 were checked which showed that out of forty-one derivatives, twentyeight derivatives were showed more potency as compared to the standard D-saccharic acid 1,4-lactone (IC50 = 48.40 ± 0.25 μM). Among which compound 103 (IC50 = 1.10 ± 0.10 μM) was the most potent compound while compounds 102, 89, 116, 96, 110, and 111 were also the potent about ten to twenty fold better than standard. These derivatives were also evaluated for their urease inhibitory activity. Compound 78, 88, 92, 106, and 116 showed good to moderate potential against urease as compared with the standard thiourea, while remaining derivatives were found to be non-active. Ten Compounds 78, 80, 87, 90, 96, 97, 104, 106, 111, and 115 were showed more antiinflammatory potency than the standard ibuprofen. Out of 98 synthesized derivatives of pyridine, 29 compounds 25, 28, 31, 34, 43, 45, 48, 49, 55, 57, 58, 60, 61, 69, 71, 72, 74, 75, 83, 89, 97, 98, 102, 103, 109, 110, 111, 112, and 116 were new compounds. Chapter 2 describes introduction of pyrimidine, its biological background and various synthetic protocols. In addition, it also deals with the rationale behind the current study. One pot three-component synthesis was adopted to synthesized Dihydropyrimidone derivatives (150-189) and screened for in vitro biological evaluation. Forty synthetic derivatives of dihydropyrimidones were screened for antiinflammatory activity. Six derivatives 151, 157, 160, 162, 166, and 182 were found to be active and showed more significant to less significant activity in the comparison of standard ibuprofen. All of these derivatives were found to be inactive in intiglycation assay and against tyrosinase enzyme. All derivatives were also screened for their in vitro β-glucuronidase inhibitory activity. Among forty analogs, eighteen compounds 157-159, 162-166, 171-178, 181, and 182 were possess more inhibitory potential than the standard D-saccharic acid 1,4lactone (IC50 = 48.4 ± 1.25 μM). In DPPH activity, only one compound 162 is active which is two-fold more potent than the standards BHT (IC50 = 128.2 ± 0.5 µM) and remaining compounds were found to be inactive.