Biological Role of Chalcones in Medicinal Chemistry

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

Self-Assembled Lipid Cubic Phase and Cubosomes for the Delivery of Aspirin as a Model Drug

Three-dimensionally organized lipid cubic self-assemblies and derived oil-in-water emulsions called “cubosomes” are attractive for various biotechnological applications due to their ability to be loaded with functional molecules and their associated sustained release properties. Here, we employed both of these lipid-based systems for the delivery of a model drug, aspirin, under comparable conditions. Studies were performed by varying drug-to-lipid ratio and the type of release medium, water and phosphate buffer saline (PBS). Release rates were determined using UV−vis spectroscopy, and small-angle X-ray scattering was used to confirm the type of self-assembled nanostructures formed in these lipid systems. The release from the bulk lipid cubic phase was sustained as compared to that of dispersed cubosomes, and the release in PBS was more efficient than in water. The tortuosity of the architecture, length of the diffusion pathway, type of nanostructure, and physicochemical interaction with the release media evidently contribute to these observations. This work is particularly important as it is the first report where both of these nanostructured lipid systems have been studied together under similar conditions. This work provides important insights into understanding and therefore controlling the release behavior of lipid-based drug nanocarriers

Base and Catalyst-Free Synthesis of Nitrobenzodiazepines via a Cascade NNitroallylation- Intramolecular Aza-Michael Addition involving o-Phenylenediamines and Nitroallylic Acetates

Published ArticleA [4+3] annulation of o-phenylenediamines with primary nitroallylic acetates affords nitrobenzodiazepines (NBDZs) in good to excellent yield. The reaction which proceeds in MeOH at room temperature in the absence of any base or catalyst involves a cascade SN2 Nnitroallylation- intramolecular aza-Michael addition sequence. In the case of mono-N-arylated ophenylenediamines and o-aminobenzamides, the reaction stops at the SN2 stage affording nitroallylic amines. On the other hand, reaction of o-aminobenzamides with secondary nitroallylic acetates delivers SN2’ products. Formation of stable SN2 and SN2’ products provides insights into the reactivity of primary and secondary nitroallylic acetates and also the mechanism of formation of nitrobenzodiazepines

Novel Synthesis of benzyl-Methoxyl Protected Aspalathin Analog via C-Glucosylation of Pentamethoxy Dihydropropane

The first report on a novel and efficient synthesis of benzyl-methoxy protected aspalathin derivative has been described via C-glucosylation of pentamethoxy dihydropropane. The synthesized compound was characterized by 1H, 13C NMR, COSY, and HSQC techniques

Efficacy and pharmacokinetic evaluation of a novel anti-malarial compound (NP046) in a mouse model

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 10mg/kg using oral gavage and IV at 5 and 1mg/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 10mg/kg) and IV (5mg/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 50mg/kg and 10mg/kg dose, respectively and a moderate mean half-life ranging from 3.1 to 4.4hours. 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

(Mes-Acr-Me)+ClO4– Catalyzed Visible Light-Supported, One-Pot Green Synthesis of 1,8-Naphthyridine-3-Carbonitriles

A novel, four-component one-pot green synthesis of biologically active 1,8-naphthyridines by a reaction of diverse aromatic aldehyde, malononitrile, 4-hydroxy substituted 1,6-dimethylpyridin-2(1H)-one, corresponding aniline in EtOH catalyzed by 9-Mesityl-10-methylacridinium perchlorate [(Mes-Acr-Me)+ClO4–] under visible light generated from a 24 W Blue LED wavelength 450–460 nm at 26 °C is reported. In contrast with the reported procedure, our methodology is diverse, versatile and has several favourable factors such as metal-free, excellent yields, shorter reaction durations, chromatography free and straightforward extraction process

Synthesis, Characterization and Antimicrobial Properties of Novel Benzimidazole Amide Derivatives Bearing Thiophene Moiety

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

The Nano-Based Catalyst for the Synthesis of Benzimidazoles

The properties of benzimidazole and its derivatives have been studied over more than one hundred years. The benzimidazole ring is an important pharmacophore in modern drug discovery. Benzimidazole-based compounds possess potential application as medicinal drugs, presently; more than 20 drugs are available for the treatment of different diseases. Also, this motif is considered as privileged structure in medicinal chemistry because of its wide range of biological activities viz., antibacterial, antifungal, anticonvulsant, anti-tubercular, anti-HIV, anti-diabetic, anti-oxidant, anticancer, anti-inflammatory, analgesic antileishmanial, and antihistaminic agents etc. Owing to the diverse therapeutic applications, the incorporation of benzimidazole nucleus has become a field of high interest to organic and medicinal chemists. The various key starting materials (KSMs) utilized includes, aromatic and heteroaromatic 2-nitro-amines, phenylenediamine, carboxylic acids or its derivatives. However, these classical methods suffer from demerits such as, low atom economy, the formation of by-products, harsh reaction conditions, extended reaction period, expensive catalysts, and unsatisfactory yield of products as well as toxic solvents. Hence, the chemists have their attention towards developing synthetic processes primarily based on the set of principles of green chemistry. In this context, many efficient methods were developed for the synthesis of benzimidazole using the nanocatalyst or nanostructures. In this review, special emphasis has been given to discuss the “green” synthetic techniques adopted for the preparation of functionalized benzimidazole congeners as well as key mechanistic considerations and future outlook in this area. In this review, the literature up to the November 2021 in which very recently reported synthetic routes to access benzimidazole scaffolds are discussed. We are focused on, in particular, the synthetic methodologies/routes to construct 2-substituted/1,2-disubstituted benzimidazole or benzimidalones via various protocols involving condensation, cyclization, metal-free conditions, solvent-free conditions, and using nanocatalyst. This review will further aid the researcher to in developing more efficient and facile methods for the synthesis of benzimidazoles and associated hybrids

Synthesis, Characterization, and Antibacterial Activity of Novel Poly-3-butyl Thiophene Embedded TiO2@ZnO Hybrid Nanocomposites

In the present work, TiO2@ZnO nanoparticles (NPs) (10 wt% and 15 wt%) were decorated over poly-3-butyl thiophene (P3BT) and obtained as novel hybrid nanocomposites. The synthesized hybrid nanocomposites studied for crystalline phase, microstructure, zeta potential, water contact angle, and their antibacterial activity were evaluated by a zone of inhibition against S. bacillus and E. coli bacterial cells by disc diffusion method. The in vitro antibacterial activity results were compared with the standard drug ciprofloxacin as well as results obtained from statistical analysis. The surface dispersion and stability of the NPs were examined by water contact angle measurement and zeta potential studies. Irregular morphology was observed as TiO2@ZnO NPs concentration increased on P3BT polymer, and phase analysis revealed the mixed composition of hexagonal crystal structure. Redshift in optical absorption spectra resulted in TiO2@ZnO concentration increases on P3BT polymer. An increase in hydrophobicity with the increase in Rrms value was observed as TiO2@ZnO NPs concentration increases. It was found that P3BT:TiO2@ZnO (10 wt% and 15 wt%) hybrid nanocomposites displayed greatly improved antibacterial activity against S. bacillus and E. coli bacterial cells when compared with TiO2@ZnO NPs. The P3BT:TiO2@ZnO hybrid nanocomposites showed high stability in basic solution, better hydrophobicity, and large surface area. The results of antibacterial property studies are compared with statistical results and are in good agreement with each other exhibiting TiO2@ZnO:P3BT hybrid nanocomposites acting as a better candidate for antimicrobial therapy

Facile Synthesis of Chitosan-ZnO-α-Fe2O3 as Hybrid Nanocatalyst and Their Application in Nitrothiopheneacetate Reduction and Cyclization of Aminothiopheneacetate

In the present research work, two films of Chitosan-ZnO-α-Fe2O3 nanocatalyst were synthesized by sol gel method using ZnO and Fe2O3 in equimolar concentration along with chitosan. The synthesized catalysts were characterized by fourier-transform infrared spectroscopy, ultraviolet–visible spectroscopy (UV–Vis), X-ray diffraction, field emission scanning electron microscopy and energy dispersive X-ray spectroscopic methods. Morphological studies revealed spongy spherical shaped nanoparticles in both film (A and B) having nanoparticle size 25 nm and 39.5 nm. The synthesized films were employed as a catalyst for reduction of nitrothiophene acetate along with Fe/FeSO4 and the reaction completion was monitored by TLC and UV–Visible spectral analysis. The reduction yield was 79% and 88% respectively for both the film A and film B. Further, the cyclization of formed aminothiophene with trimethylaluminum lead to the formation of dihydrotheinopyrrolone, which was confirmed by liquid chromatography with mass spectral detector and proton nuclear magnetic resonance (1H-NMR) spectroscopic characterization techniques. Thus, the result indicates that the synthesized Chitosan-ZnO-α-Fe2O3 nanocatalysts are efficient over other traditional catalysts for effective reduction of nitro group