Vol 53, No 3 (2019)

Benzimidazole ring system is well known for its potential for various biological activities. Recent research works have indicated the excellent antiviral potential of various derivatives of this heterocycle. Depending upon the nature of substitution and side chain functionalities, benzimidazole derivatives exhibit anti-HCV, anti-HBV, anti-HIV, anti-HSV, anti-Coxsackie virus, anti-rotavirus, anti-mosquito larvae, anti-PRSV, anti-adenovirus, anti-tobacco mosaic, and anti-Sunn-hemp rosette viruses, etc. In this article, the recent literature available on antiviral benzimidazole derivatives is summarized. The article could be useful in designing new antiviral agents based on this ring system.

Flavonoid glycosides that are present in acylated form have good prospect to be developed into therapeutic agents due to their improved biological properties, stability and physico-chemical properties compared to their maternal compounds. The present study aimed to compare the free radical scavenging and cytotoxic activities of a series of acylated and non-acylated kaempferol glycosides isolated from Stenochlaena palustris. The in silico binding interactions of the most cytotoxic glycoside with epidermal growth factor receptor was also evaluated. Results indicated that the free radical scavenging capability and cytotoxicity of kaempferol 3-O-β-D-glucopyranoside were enhanced through acylation with selected hydroxycinnamoyl groups, whereas mono-acylation did not improve both activities. Molecular docking study revealed that di-acylation was essential for the compound to bind to five major active sites of the receptor. Kaempferol 3-O-β-D-glucopyranosides that are di-acylated may be further explored for their chemopreventive and anticancer properties due to their significant antioxidant and cytotoxic properties.

3-Acyloxy-5-aryl-7-bromo-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (3 – 18) were synthesized and shown to possess (ED₅₀ = 0.05 – 5 mg/kg) hypnotic, sedative, anticonvulsant, and anxiolytic properties. The hypnotic activity of the tested compounds varied in the dose range 0.22 – 1.50 mg/kg i.p. in mice. The pharmacological properties of 3 – 14 were comparable to those of cinazepam (Levana^® IC) and its metabolite 3-hydroxyphenazepam. The CBDR affinity was shown to increase with acyl length in the series C2-C5 whereas it decreased significantly in the series C6-C8. The tested compounds were characterized by low toxicity with LD₅₀ > 650 mg/kg i.p. in mice.

New fluorenecarboxylic acid derivatives (structural analogs of amizil) were synthesized. A compound with low toxicity (LD₅₀ = 45 ± 9.9 mg/kg) and antidepressant and antianxiety effects was identified. The central and peripheral muscarinic anticholinergic properties of 2-dimethylaminoethyl 9-hydroxyfluorene-9-carboxylate were studied using an arecoline tremor model. Apharmacological analysis showed that the new amizil structural analog exhibited pronounced central muscarinic anticholinergic activity and did not possess peripheral muscarinic anticholinergic effects. The advantages of the tested compound over amizil, amitriptyline that is widely used in the clinic, and the benzodiazepine tranquilizer diazepam were discussed. The results indicated that 2-diethylaminoethyl 9-hydroxyfluorene-9-carboxylate was promising for further development for the treatment of depressive and anxiety disorders.

High-throughput screening identified a new class of antibacterial compounds based on N-pyridyl-substituted p- and m-carboxypiperidine amides. Constructs with the two reporter genes RFP and Katushka2S allowed the detection of compounds that inhibit protein translation against DNA biosynthesis. Some agents of this class demonstrated antibacterial activity by inhibiting translation. The most promising compound had an MIC of 12 μg/mL. Thus, this class could become a valuable platform for developing new compounds with higher antibacterial activity and selectivity.

Natural deep eutectic solvents (NADES) are promising green solvents for extracting biologically active compounds from plant raw material. This is the first study in which NADES were used to extract phlorotannins from brown algae Fucus vesiculosus L. and Ascophyllum nodosum (L.) Le Jolis. The extraction efficiency of polyphenols was evaluated using 10 NADES based on choline chloride, lactic acid, betaine, and glucose in various mole ratios. The effect of H₂O in aqueous solutions of NADES on extraction of phlorotannins was studied. Algae were extracted by maceration for 120 min at 50°C with a 1:5 raw-material:extractant ratio. Phlorotannins were quantified by spectrophotometry using the Folin–Ciocalteu method. The maximum extraction of phlorotannins (60 – 72%) was achieved using aqueous NADES solutions (50 – 70%) based on choline chloride with added lactic or malic acid and also on malic acid and betaine. The NADES had efficiencies comparable to Me₂CO and EtOH.

A quantitative HPLC method was developed for analyzing mefebut in pharmacokinetic studies. The method was highly sensitive and selective and could be used for determinations in bioassays. The optimized sample-preparation method did not significantly influence the standard error of the quantitative determination.

Novel thiocoumarins and quinolin-2-ones were synthesized and screened for anticonvulsant activity. The structure–activity relationship of a series of synthesized compounds and previously prepared coumarin derivatives was analyzed. The methyl ester of N-(3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-4-aminobutyric acid (3a) at a dose of 12.5 mg/kg (i.p.) had the greatest anticonvulsant activity in mouse tests.

Aqueous extracts of nettle leaves (100 mg/kg) and greater burdock roots (25 mg/kg) decreased the blood levels of glucose, triglycerides, total cholesterol, and low- and very-low-density lipoproteins; increased the cholesterol and protein contents of high-density lipoproteins; and prevented low-density lipoprotein oxidation and high-density lipoprotein and hemoglobin glycosylation in experimental diabetes mellitus induced in rats by streptozotocin and a high-fat (30%) diet. The hypolipidemic action of the plant extracts did not decrease if the animals were fed a high-fat diet. Rosiglitazone exhibited more significant hypoglycemic and hypolipidemic effects with a low-fat diet. Flavonoids and carotenoids were responsible for the antidiabetic action of the nettle and burdock extracts.

Zoledronic acid is the drug substance of the highly efficient antiresorptive medicine Zometa. An improved synthesis of zoledronic acid via bis-phosphonation of 2-(1H-imidazol-1-yl)acetic acid is reported.

Method development for determining prekallikrein activator in medicinal preparations of human immunoglobulins and albumin found that the adequacy of chromogenic determination of prekallikrein activator depends on the activity of the used prekallikrein reagent, the quantitative component ratio in the reaction mixture and its incubation time, and the concentration of employed chromogenic reagent. Acceptance criteria for commercial prekallikrein reagents are justified. The main method parameters and validation test results confirming the linearity in the range 0 – 35 IU/mL, accuracy, and intralaboratory precision are presented and correspond to those for biological analytical methods. The elaborated method can be used for quality assessment of prekallikrein activator content in medicinal preparations of human immunoglobulins and albumin.

There is an error in the association of the author names and affiliations.

The names and affiliations are:

Muhammad Azhar Abbas,¹ Afeefa Aslam,² Mudassir Iqbal,^3,* Sajid Bashir,³ Tahir Mehmood,⁴ and Joerg Kressler⁵