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Coronavirus disease 2019 (Covid-19), a serious disease caused by the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), was firstly identified in the city of Wuhan of China in December 2019, which then spread and became a global issue due to its high transmission rate. To date, the outbreak of COVID-19 has resulted in infection to 230,868,745 people and the death of 4,732,669 patients. It has paralyzed the economy of all the countries worldwide. Considering the possible mutations of SARS-CoV-2, the current medical emergency requires a longer time for drug design and vaccine development. Drug repurposing is a promising option for potent therapeutics against the pandemic. The present review encompasses various drugs or appropriate combinations of already FDA-approved antimalarial, antiviral, anticancer, anti-inflammatory, and antibiotic therapeutic candidates for use in the clinical trials as a ray of hope against COVID-19. It is expected to deliver better clinical and laboratory outcomes of drugs as a prevention strategy for the eradication of the disease.

Chalcones are promising synthons and bioactive scaffolds of great medicinal interest due to their numerous pharmacological and biological activities. They are well recognized to possess antimicrobial, anticancer, antitubercular, antioxidant, anti-inflammatory, antileishmanial, and other significant biological activities. This chapter highlights recent updates and applications of chalcones as biologically, pharmacologically, and medicinally important entities.

In the present investigation, novel amide derivatives of benzimidazole (4a-f) with different thiophene acids (a-f) coupled in the presence of 1-[Bis (dimethylamino) methylene]-1H-1, 2, 3-triazolo [4, 5-b] pyridinium 3-oxide hexafluorophosphate (HATU) reagent at room temperature and as-synthesized derivatives were characterized by (1H-NMR and 13C-NMR) proton and carbon magnetic resonance, and high-performance liquid chromatography (HPLC) analytical techniques. The amide derivatives were tested for in vitro antimicrobial and antifungal activity and ciprofloxacin was used as standard. The antifungal activity was tested with Carbendazim and Fenbendazole cell lines using clotrimazole standard drug. The results indicated the potential activity toward S. bacillus with compounds having IC 50 of 4 (a), 4 (b), 4 (d) and 4 (e) against antimicrobial strains with IC50 of 51.8 μm, 57.4 μm, 54.5 μm and 56.5 μm respectively. However, compounds 4 (a), 4 (c) and 4 (d) showed greater inhibitions against Carbendazim fungal cell line with IC50 of 22.9, 26.8 and 28.8 μm. On the other hand IC50 values of the Fenbendazole for compounds 4 (a), 4(c) and 4 (d) were found to be 12.7, 10.2 and 12.7 μm, respectively. The thiophene-substituted benzimidazole amide derivatives are the potential candidate drug for antibacterial and antifungal activity.

Malaria remains a great burden on humanity. Although significant advances have been made in the prevention and treatment of malaria, malaria control is now hindered by an increasing tolerance of the parasite to one or more drugs within artemisinin combination therapies; therefore, an urgent need exists for development of novel and improved therapies. The University of the Free State Chemistry Department previously synthesized an antimalarial compound, NP046. In vitro studies illustrated an enhanced efficacy against Plasmodium falciparum . However, NP046 showed low bioavailability. Efforts to enhance the bioavailability of NP046 have resulted in the synthesis of a number of aminoalkylated diarylpropanes, including NP085 and NP102. Pharmacokinetic studies were conducted in C57BL/6 mice, with 15 mg/kg NP085 or NP102 administered orally and the 5 mg/kg NP085 or NP102 administered intravenously. Blood samples were collected by means of tail bleeding at predetermined time intervals. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and subsequently pharmacokinetic modeling was done for both compounds. NP085 and NP102 were incubated in vitro with human and mouse liver microsomes. Both compounds were also subjected to a parallel artificial membrane permeation assay. In vitro studies of NP085 and NP102 illustrated that both of the compounds are rapidly absorbed and undergo rapid hepatic metabolism. The maximum concentration of drug ( C max ) obtained following oral administration of NP085 and NP102 was 0.2 ± 0.4 and 0.7 ± 0.3 μM, respectively; the elimination half-life of both compounds was 6.1 h. NP085 and NP102 showed bioavailability levels of 8% and 22%, respectively.

Background Even though malaria is a completely preventable and treatable disease, it remains a threat to human life and a burden to the global economy due to the emergence of multiple-drug resistant malaria parasites. According to the World Malaria Report 2013, in 2012 there were an estimated 207 million malaria cases and 627,000 deaths. Thus, the discovery and development of new, effective anti-malarial drugs are required. To achieve this goal, the Department of Chemistry at the University of the Free State has synthesized a number of novel amino-alkylated chalcones and analogues, which showed in vitro anti-malarial activity against both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. The lead compound (NP046) was selected for a comprehensive pharmacokinetic (PK) and in vivo efficacy evaluation in a mouse model. Methods In vivo efficacy: Water solutions of NP046 were administered orally at 50 and 10 mg/kg using oral gavage and IV at 5 and 1 mg/kg via the dorsal penile vein to Plasmodium berghei (ANKA strain) infected male C57BL/6 mice (n = 5), once a day for four days. Blood samples were collected via tail bleeding in tubes containing phosphate buffer saline (PBS) on day five to determine the % parasitaemia by flow cytometry. In vivo PK: NP046 solutions in water were administered orally (50 and 10 mg/kg) and IV (5 mg/kg) to male C57BL/6 mice (n = 5). Blood samples were collected via tail bleeding into heparinized tubes and analysed using a validated LC-MS/MS assay. Data obtained from the concentration-time profile was evaluated using Summit PK software to determine the PK parameters of NP046. Results NP046 inhibited parasite growth for the oral and IV groups. Better parasite growth inhibition was observed for the IV group. The PK evaluation of NP046 showed low oral bioavailability (3.2% and 6% at 50 mg/kg and 10 mg/kg dose, respectively and a moderate mean half-life ranging from 3.1 to 4.4 hours. Conclusion Even though the oral bioavailability of NP046 is low, its percentage parasite growth inhibition is promising, but in order to improve the oral bioavailability, structure-activity-relationship (SAR) optimization studies are currently being conducted. Electronic supplementary material The online version of this article (doi:10.1186/1475-2875-14-8) contains supplementary material, which is available to authorized users.