Radiopharmaceuticals: On-Going Research for Better Diagnosis, Therapy, Environmental, and Pharmaceutical Applications

Radiopharmaceutical material is a pharmaceutical product or drug that may exert spontaneous degradation of unstable nuclei with nuclear particles or photons emission. Radiopharmaceuticals may be used in research, diagnosis, therapy, and environmental purposes. Moreover, radiopharmaceuticals act as radioactive tracers among patients via gamma-ray emissions. Therefore, the uses of radiopharmaceuticals as diagnostic agents may be given to patients to examine any biochemical, molecular biology, physiological, or anatomical abnormalities. Therapeutic radiopharmaceutical may be administered internally for therapeutic purposes via selective effect on certain abnormal cells or organs. The best known example for therapeutic radiopharmaceuticala is iodide131 for thyroid ablation in among patients with hyperthyroid. A third class of radiopharmaceutical is drug labeling which mainly used in research by using small amount of radioactive substances not for diagnostic purposes, but to investigate the metabolism, bio-distribution, pharmakodynamic, and pharmakokinetic of certain drugs in a nonradioactive form. This chapter focuses mainly on basic fundamentals of radiopharmaceutical chemistry, preparation, environmental, pharmaceutical, diagnostic, therapeutic, and research applications

Lipoprotein (a), Lipid Profile and Mean Platelet Volume in Hypothyroid Patients in Sana'a, Yemen: A Case-Control Study

Objectives: This study aimed to measure lipoprotein (a) [Lp(a)], lipid profile and mean platelet volume (MPV) in hypothyroid patients compared to healthy controls.Methods: An unmatched case-control study was conducted involving 100 subjects (50 overt hypothyroidism patients and 50 healthy controls admitted to the University of Science and Technology Hospital, Al-Thawra Hospital and Al-Jomhori Hospital- Sana'a, Yemen during the period from May 2013 to March 2014. Data were collected by in-person interview using a structured questionnaire followed by weight and height measurements. Fresh blood samples were collected and analyzed using electrochemiluminescent, spectrophotometric and immunoturbidimetric methods for estimating Lp(a), lipid profile and MPV parameters.Results: Hypothyroid patients had a significantly higher concentration of Lp(a) compared to the control. Total cholesterol (TC), triglycerides and low-density lipoprotein-cholesterol (LDL-C) levels were also significantly higher in hypothyroid patients. Serum level of free triiodothyronine (FT3) was negatively correlated with Lp(a), TC and LDL-C (r=–0.380, p=0.007; r=–0.354, p=0.012; r=–0.350, p=0.013, respectively). However, serum thyroid-stimulating hormone was positively correlated with Lp(a), TC and LDL-C (r=0.344, p=0.015; r=0.299, p=0.035; r=0.405, p=0.004, respectively) among hypothyroid patients. MPV levels, on the other hand, showed a strong positive correlation with (r=0.611, p=0.001).Conclusions: These findings indicate that overt hypothyroidism patients tend to have increased Lp(a) and atherogenic lipids that may contribute to increasing risk of atherosclerosis. However, hypothyroid patients showed no significant difference compared to the controls regarding the MPV

Drug Repurposing in Dermatology: Molecular Biology and Omics Approach

The withdrawal of several blockbuster drugs due to severe adverse effects and the failure of several developed drugs in clinical trials raised questions about the efficacy of current approaches of drug discovery. Moreover, the limitation of resources and the long and costive process of drug discovery made a lot of pharmaceutical companies to employ drug repurposing strategies to get new insights about activities that were not considered during their initial discovery. The development of therapeutics for treatment of dermatological condition is not considered as priority although it affects the lifestyle of thousands of people around the world. Serendipity and observations have contributed significantly in this field but immerse efforts have been exerted to find systematic methods to identify new indications for drugs, especially with the unprecedented progress in molecular biology and omics. So, in this chapter, we will emphasize on different approaches used for drug repositioning and how it was applied to find new therapeutics for different dermatoses

Perspective Chapter: Integrated Network Pharmacology and Multiomics Approach to Elucidate the Repositioning of Fatal Food Toxins to Lifesaving Anticancer Drug

This research investigates repurposing potato glycoalkaloids as lifesaving anticancer drugs. There is integration of network pharmacology with multiomics. Solanine, chaconine, and their hydrolysis products’ pharmacokinetics were tested using SwissADME. Solanine and chaconine targets were identified via reverse pharmacophore mapping. Through database mining, 26 solanine and chaconine targets were found in cancer genes. To understand gene function, KEGG and GO analyses were done. STRING was used to create a protein-protein interaction network to find similarities between chemicals and cancer. To find prognostic genes in various cancers, CytoHubba in Cytoscape identified hub genes and GEPIA2 did survival analysis. ADME testing for solanine and chaconine medication candidates failed. Their glycosylation boosted solubility and P-glycoprotein inhibition. Cancer targets shared by both drugs were elevated in cancer-related pathways such as Pi3k-Akt1 and HIF-1. Cell death control and programmed cell death genes were enriched in gene ontology study. We built a protein-protein interaction network with 26 nodes and 38 edges. The hub genes were STAT3, TLR4, FGF2, IL2, NFKB1, AR, CHUK, TRIM24, NOS3, and KDM1A. Survival research showed that these genes predict cancer prognosis. We found that solanine and chaconine may interact with cancer-related genes to fight cancer. Discovery of hub genes with prognostic significance sheds light on glycoalkaloids’ anticancer processes

Metformin: A Small Molecule with Multi-Targets and Diverse Therapeutic Applications

Metformin is one of the most prescribed agents in the treatment of type 2 diabetes. Its history goes back to the use of goat’s rue (Galega officinalis Linn., Fabaceae). G. officinalis is rich in galegine, a guanidine derivative with a blood glucose-lowering effect. Research based on the effects of guanidine rich on this traditional herbal medicine led to the development of metformin. Metformin continues to serve as a multi-target drug. Its benefits for treating/controlling several diseases were thoroughly discovered over time. These include health disorders such as cancers, obesity, periodontitis, cardiovascular, liver, skin, and renal disorders. Moreover, there is evidence to propose that metformin postpones the aging processes as well as modulates the microbiota to promote better health. So far, it is not fully understood, how metformin can accomplish such pleiotropic pharmacological and therapeutic effects. Metformin may decrease malignancy via suppressing the signal of insulin/IGF-1, avoiding the release of cytokines via NF-κB, and increasing the immune reaction to cancer cells. This chapter discusses the history of metformin discovery, chemistry, its role in diabetic patients, and proposed molecular mechanisms to shed more light on the diverse effects and its ability to target multiple signaling pathways

Cytotoxic activity of silver nanoparticles prepared from Psidium guajava L. (Myrtaceae) and Lawsonia inermis L. (Lythraceae) extracts

Purpose: To biosynthesize silver nanoparticles (AgNPs) using Psidium guajava L. and Lawsonia inermis L. leaf extracts, and investigate their antioxidant and cytotoxic activities.Methods: The aqueous extracts were prepared by maceration in distilled H2O followed by partitioning with EtOAc. AgNPs were prepared by treating the extracts with 1 mM AgNO3 and then were characterized by UV-vis and FTIR analyses, and transmission electron microscopy (TEM). MTT cytotoxicity and 2,2`-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) antioxidant assays were used to assess their cytotoxic and antioxidant properties, respectively.Results: AgNPs from P. guajava and L. inermis extracts exhibited good morphological stability and showed moderate antioxidant activity (68.1 and 71.9%, respectively) compared to their extracts. Equipotent cytotoxicity against HCT-116 and MCF-7 cells was observed for AgNPs derived from P.guajava, while AgNPs derived from L. inermis possessed two-fold cytotoxicity compared to their corresponding extracts. Phytochemical analysis of P. guajava afforded pyrogallol, quercetin, quercetin-3-O-β-xylopyranoside, quercetin-3-O-β-arabinopyranoside, and quercetin-3-O-α-rabinofuranoside, while L. inermis afforded lawsone and luteolin.Conclusion: Flavonoids and phenolics play a major role in reducing Ag+ ions, surface coating, antioxidant, and cytotoxic activities of AgNPs. The biocompatible AgNPs produced by L. inermis demonstrate promising cytotoxic activity that could contribute to new cancer treatments

Synthesis and antitumor testing of certain new fused triazolopyrimidine and triazoloquinazoline derivatives

AbstractNew series of 1,2,4-triazolopyrimidine and 1,2,4-triazoloquinazoline derivatives were designed, synthesized, and evaluated for their antitumor activity. Compounds 6, 11, 26, 29, 41, 44, 48, 49 and 58 were tested as antitumor agents by the use of DNA-binding assay on TLC-plates, colorimetric assay for the degree of DNA-binding (Methyl green-DNA displacement assay), evaluation of antineoplastic activity against Ehrlich Ascites Carcinoma in mice, and finally modulation of apoptosis. 5-Flurouracil, vitamin C and ethidium bromide were used as positive controls in these techniques. Compound 26 proved to be the most active member of these series as antitumor agent with IC50 value of 47±1. Several characteristic features were observed to be essential for activity such as the morpholine group and the phenylazo group, in addition the electron-withdrawing groups favor the activity than the electron-donating ones

A comparative study on the efficacy of artesunate plus sulphadoxine/pyrimethamine versus artemether-lumefantrine in eastern Sudan

BACKGROUND: A combination of artesunate (AS) plus sulphadoxine/pyrimethamine (SP) as first-line and artemether-lumefantrine (AL) as second-line treatment are currently recommended against uncomplicated P. falciparum infection in Sudan. However, there is limited information on the efficacy of ACTs in the country and only one report of PCR-corrected results for AS/SP only. METHODS: The WHO protocol for the assessment of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria was employed. Artesunate plus sulphadoxine/pyrimethamine (AS/SP) was compared to artemether-lumefantrine (AL) in a 28-day follow up. Samples that were classified as early treatment failure (ETF), late treatment failure (LCF) or late parasitological failure (LPF) were genotyped for msp-1 and msp-2 genes to differentiate recrudescence from reinfection. RESULTS: A total of 178 patients were screened and 160 met the enrollment criteria and were recruited to the study of which 157 (98.1%) completed the follow up and had an analysed treatment outcome. On the AS/SP arm, three (0.038%) patients were lost during the follow-up, two on day 1 and one on day 7, and 77 (96.3) completed the study, while all 80 (100%) patients completed the follow up in the AL arm. In the per protocol analysis for AS/SP the treatment outcome for patients who completed the follow-up were as follows: adequate clinical and parasitological response (ACPR); 84.4% ETF; 1.3%, LCF; 3.9%, (LPF); 10.4%. For the AL arm the out come was as follows, ACPR; 90%, ETF; 0%, LCF; 6.3% and LPF; 3.8%. However, when PCR-corrected, 6.5% (5/77) of patients treated with AS/SP maintained parasites from their primary infection, while (7/80) in the AL group maintained their initial parasite genotype. Therefore, PCR-corrected efficacy was 93.5% in the AS/SP treated group and for AL it was 91.3%. CONCLUSION: Both AS/SP and AL are highly effective for the treatment of uncomplicated falciparum malaria in eastern Sudan. However, AS/SP appears to have a slightly higher efficacy than AL, this may be due to patient compliance with the repeated dose rather than drug efficacy