Synthesis and Biological Evaluation of (E)-N’-Benzylidene-7-methyl-2-propyl-1H-benzo[d] imidazole-5-carbohydrazides as Antioxidant, Anti-inflammatory and Analgesic agents
Abstract:Abstract(E)-N’-Benzylidene-7-methyl-2-propyl-1H-benzo [d]imidazole-5-carbohydrazides (5a-r) have been synthesized from 7-methyl-2-propyl-1H-benzo[d]imidazole-5-carbohydrazide (3) by condensing with different aromatic aldehydes (4a-r). Title compounds (5a-r) were evaluated for in vitro antioxidant activity and based on their potential for antioxidant property, selected compounds 5d and 5m-p were screened for in vivo anti-inflammatory and analgesic activity. The results indicate that the compound 5o and 5p are e… Show more
“…[8,9] Azoles possessed distinct structural importance due to their capability of making hydrogen bonds and other non-covalent interactions with target sites of various enzymes. These small heterocyclic moieties are incorporated in structural framework of different anti-proliferative, [10] anti-inflammatory, [11,12] anticancer, [13,14] antimicrobial, [15] anti-tubercular agents. [16,17] Many nitrogen atom containing azolic templates have recently been reported as antiurease agents as well.…”
Towards discovery of effective urease inhibitors; we disclose here a hybrid series of imidazole and pyrazole motifs as potent antiurease agents. A para-toluenesulfonic acid (TsOH) catalyzed, facile synthetic approach was employed for the preparation of targeted molecular designs in good yields upto 94 %. The novel scaffolds were characterized by different spectroscopic means (FTIR, NMR, and Mass spectrometry) and elemental analysis helped to identify the purity of these compounds. Afterwards, the derivatives was tested against Jack bean's urease enzyme to explore their inhibiting potencies. All analogues (4 a-4 l) were found active against the studied enzyme in comparison with the standard drug thiourea (IC 50 = 21.26 � 0.12 μM). However, following dibromo substituted derivatives: 4 f, 4 g, 4 h, 4 i, 4 j, 4 k, and 4 l were surfaced out as potent urease inhibitors among the series. The identified lead candidates were meta-nitro substituted 4 k with IC 50 = 0.7 � 0.002 μM and a para-nitro containing compound 4 l with IC 50 = 1.0 � 0.003 μM. As observed in docking calculations, ionic and hydrogen bonding, π-stacking, interaction with nickel ions and other hydrophobic interactions probably stabilized the ligand bindings at the active site of urease.
“…[8,9] Azoles possessed distinct structural importance due to their capability of making hydrogen bonds and other non-covalent interactions with target sites of various enzymes. These small heterocyclic moieties are incorporated in structural framework of different anti-proliferative, [10] anti-inflammatory, [11,12] anticancer, [13,14] antimicrobial, [15] anti-tubercular agents. [16,17] Many nitrogen atom containing azolic templates have recently been reported as antiurease agents as well.…”
Towards discovery of effective urease inhibitors; we disclose here a hybrid series of imidazole and pyrazole motifs as potent antiurease agents. A para-toluenesulfonic acid (TsOH) catalyzed, facile synthetic approach was employed for the preparation of targeted molecular designs in good yields upto 94 %. The novel scaffolds were characterized by different spectroscopic means (FTIR, NMR, and Mass spectrometry) and elemental analysis helped to identify the purity of these compounds. Afterwards, the derivatives was tested against Jack bean's urease enzyme to explore their inhibiting potencies. All analogues (4 a-4 l) were found active against the studied enzyme in comparison with the standard drug thiourea (IC 50 = 21.26 � 0.12 μM). However, following dibromo substituted derivatives: 4 f, 4 g, 4 h, 4 i, 4 j, 4 k, and 4 l were surfaced out as potent urease inhibitors among the series. The identified lead candidates were meta-nitro substituted 4 k with IC 50 = 0.7 � 0.002 μM and a para-nitro containing compound 4 l with IC 50 = 1.0 � 0.003 μM. As observed in docking calculations, ionic and hydrogen bonding, π-stacking, interaction with nickel ions and other hydrophobic interactions probably stabilized the ligand bindings at the active site of urease.
“…Compound 64n shows the most potent antioxidant activity as compared to others and the results of activity were presented in (Table 24 , Katikireddy et al [ 21 ]). Scheme 24 Synthesis of ( E )-N'-(7-methyl-2-propyl-1H-benzo[ d ]imidazole-5-carbonyl)substituted formohydrazonuyl …”
Section: Main Textmentioning
confidence: 97%
“…Katikireddy et al [ 21 ] developed (E)-N'-(7-methyl-2-propyl-1H-benzo[d]imidazole-5-carbonyl) substituted formohydrazonoyl (Scheme 24 ) and evaluated for antioxidant activity using ascorbic acid as a reference drug. Compound 64n shows the most potent antioxidant activity as compared to others and the results of activity were presented in (Table 24 , Katikireddy et al [ 21 ]). Scheme 24 Synthesis of ( E )-N'-(7-methyl-2-propyl-1H-benzo[ d ]imidazole-5-carbonyl)substituted formohydrazonuyl …”
Imidazole is a five-membered heterocyclic moiety that possesses three carbon, two nitrogen, four hydrogen atoms, and two double bonds. It is also known as 1, 3-diazole. It contains two nitrogen atoms, in which one nitrogen bear a hydrogen atom, and the other is called pyrrole type nitrogen. The imidazole name was reported by Arthur Rudolf Hantzsch (1857–1935) in 1887. 1, 3-diazole is an amphoteric in nature i.e. it shows both acidic and basic properties. It is a white or colorless solid that is highly soluble in water and other polar solvents. Due to the presence of a positive charge on either of two nitrogen atom, it shows two equivalent tautomeric forms. Imidazole was first named glyoxaline because the first synthesis has been made by glyoxal and ammonia. It is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their derived products.
Various imidazole-containing compounds have been tested for their medical usefulness in clinical trials for several disease conditions. The rapid expansion of imidazole-based medicinal chemistry suggests the promising and potential therapeutic values of imidazole-derived compounds for treating incurable diseases. Imidazole core scaffold contains three carbon atoms, and two nitrogen with electronic-rich characteristics that are responsible for readily binding with a variety of enzymes, proteins, and receptors compared to the other heterocyclic rings. Herein, we provide a thorough overview of the current research status of imidazole-based compounds with a wide variety of biological activities including anti-cancer, anti-microbial, anti-inflammatory and their potential mechanisms including topoisomerase IIR catalytic inhibition, focal adhesion kinase (FAK) inhibition, c-MYC G-quadruplex DNA stabilization, and aurora kinase inhibition. Additionally, a great interest was reported in the discovery of novel imidazole compounds with anti-microbial properties that break DNA double-strand helix and inhibit protein kinase. Moreover, anti-inflammatory mechanisms of imidazole derivatives include inhibition of COX-2 enzyme, inhibit neutrophils degranulation, and generation of reactive oxygen species. This systemic review helps to design and discover more potent and efficacious imidazole compounds based on the reported derivatives, their ADME profiles, and bioavailability scores that together aid to advance this class of compounds.
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