2-substituted Benzimidazoles Research Articles

CuI/MnO2 nanocatalysed synthesis of bioactive 2-substituted benzimidazoles

This work focusses on the development and characterization of efficient CuI/MnO2 nano catalyst, characterized using XPS, XRD, EDAX, FTIR, FESEM, BET (surface area: 8.01 m2/g, a pore radius: 17.052 Å and a pore volume: 0.011 cm3/g) and TEM techniques. The reactivity of this catalyst was evaluated for the synthesis of biologically active 2-substituted benzimidazoles through condensation of o-phenylenediamine with benzaldehydes. The process features short reaction time, high TON (997.35), green conditions, high yield, easy work-up, good green metrices values such as low E-factor (0.17) and Process mass efficiency (PMI) (1.16) high Reaction mass efficiency (RME) value (91.2 %) and carbon efficiency (CE) (94 %) are good characteristics of the synthesized catalyst.

Insilico and Biological Evaluation of Anti-Inflammatory Activity of synthesized Benzimidazoles Derivatives

ABSTRACT: We have developed a mild, easy, and highly efficient green catalyst for the synthesis of 2-substituted benzimidazole. In this study, Ace-dock and DockThore performed molecular docking of the designed benzimidazole molecules with the selected protein FAAH (PDB ID: 3LJ7). We assessed the drug's likeliness (Lipinski's rule of 5) and potential toxicity using the Protox-II software. We can confidently state that the synthesized molecules adhere to Lipinski's rule of five, given that the design molecules' properties are within acceptable limits. In comparison to the reference Ibuprofen, the proposed compounds exhibited favorable pharmacokinetic properties and achieved docking scores ranging from -10.88 to -27.31 (Acedock) and -6.045 to 9.122 (DockThore). We synthesized the benzimidazole derivatives 3a to 3g. Based on an in silico study, we synthesized the molecules, chose the best ones, and then tested their anti-inflammatory action in a lab setting. We employed the albumin denaturation assay test to determine the extent of heat-induced protein denaturation inhibition. Both of the synthesized compounds and the standard drug, diclofenac sodium, inhibit denaturation of proteins at concentrations between 10 and 50 ppm. At a dose of 10 ppm, compound 3f showed the highest level of inhibition, at 70%. Diclofenac sodium exhibited the highest suppression, measuring 97.20% at a concentration of 40 ppm. We could further investigate 3F to determine its anti-inflammatory characteristics.

Comprehensive investigation of two substituted benzimidazoles: Design, synthesis, biological assessment, and characterization

Benzimidazole is a bicyclic molecule that is mostly used in medicinal chemistry. The 2-substituted benzimidazoles that are now on the market include omeprazole, flubendazole, mebendazole, and albendazole. Antioxidants are compounds that impede the oxidation process, which is the chemical process that produces free radicals. A computational technique called "in-silico screening" is used in drug discovery to effectively estimate a molecule's likelihood of interacting with a target of interest. Antihelminthics are a class of antiparasitic drugs that either kill or paralyze internal parasites like parasitic worms, all without endangering the host. A standard procedure was used to create the 2-substituted benzimidazole. PyRx software was used to do the in-silico screening for anthelmintic drugs. The DPPH and ABTS methods were used to measure the antioxidant activity. Melting point, TLC, and IR spectra were used to confirm the structures of the produced compounds. The binding affinity for sulphosalicylic acid in the anthelmentic in silico screening was -7.7. Salicylic acid demonstrated excellent antioxidant activity, as seen by its IC50 values of less than 5 mg/ml for the ABTS method and 37 mg/ml for the DPPH method. Overall, the combination of theoretical and practical yield data, along with melting points, ATR Spectra and Rf values, offers valuable insights into the synthesis and characterization of chemical compounds. The salicylic acid derivative exhibits good antioxidant activity by both the methods. The Sulphosalicylic acid derivative shows prominent In-silico anthelmintic activity result hence the synthesized compounds can be tested for anthelmintic activity in future.

TiO2/AgSbO3 nanophotocatalyst with improved photocatalytic performance in the synthesis of some benzimidazole derivatives

Due to the fact that TiO2 semiconductor has a profound surface and a porous structure, this compound shows a high photocatalytic activity among other similar counterparts. The wide band gap of TiO2 (∼3.2 eV) and existing defects in the structure of this material provides desirable efficacy to enhance absorption of visible-region of the solar energy. Therefore, introducing narrower band-gap semiconductors next to TiO2 is an effective route to expand the range of sunlight absorption in composite photocatalysts. The purpose of this research is to prepare TiO2/AgSbO3 nanophotocatalyst by the well-known hydrothermal method, then, characterized by FT-IR, XRD, EDX, DRS, and FE-SEM. After that, the nanophotocatalyst was performed in the multi-component synthesis of some pharmaceutically important 2-substituted benzimidazoles. This study confirmed that hydroxyl radical, superoxide anion radical, and holes are viable contributing mediators in the photocatalytic process. Speeding up the reaction, green nature, cost-effectiveness and non-toxicity of the nanophotocatalyst are highlight features of the present protocol.

Preparation of a novel Cu‐Ni mixed nanoparticles immobilized on clay: An Eco-friendly Nanocatalyst for mild synthesis of Benzimidazoles and pyrimidines

In the present work, Cu‐Ni mixed nanoparticles immobilized in magnetic clay (MMT-BAC@Fe3O4@CuNi) nanocatalyst were successfully synthesized using a simple method for the first time. In the design of this catalyst, nickel and copper ions were reduced and deposited on clay layers using a benzalkonium chloride directing group. The proposed method offers a safe, sustainable, and selective approach for the synthesis of 2-substituted benzimidazole and 3,4-dihydropyrimidin-2(1H)-ones using an environmentally friendly nanocatalyst. The solid catalyst was distinguished using a diversity of methods, including EDX (Energy Dispersive X-Ray), XRD (X-ray Diffraction), ICP (Inductively Coupled Plasma), VSM (Vibrating Sample Magnetometer), FT-IR (Fourier Transform Infrared Spectroscopy), TEM (Transmission Electron Microscopy) and FE-SEM (Field Emission Scanning Electron Microscopy). The significant features of this new protocol include good to excellent efficiency, oxidant-free conditions, low catalyst loading, inexpensive and non-toxic catalyst, simple procedure, moderate conditions, straightforward work-up, short reaction times, and easy reuse of the nanocatalyst.

Fe3O4@Sal-cu as a highly efficient magnetic nano-catalyst for the synthesis of 2-substituted benzimidazoles under ultrasonic irradiation and solvent free condition

Fe3O4@propyl-semicarbazide-salicyl aldehyde-Cu (Fe3O4@sal-Cu) nanocatalyst was synthesized and characterized by several methods including XRD, SEM, EDX, VSM and FT-IR analyses. The Fe3O4@sal-Cu has been used as an efficient recyclable magnetic catalyst for the preparation of benzimidazoles. The catalyst was conveniently separated from the reaction mixture by an external magnet, and could be reused without any considerable change in catalytic activity.

2D QSAR Modelling, Docking, Synthesis and Evaluation of 2-substituted Benzimidazole Derivatives as Anti-breast Cancer Agents

Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place. Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7. Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying insilico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay. Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line withIC50 values of 2.757 µg/ml and 2.875 µg/ml respectively. Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.

Magnetically recyclable nano-sized Fe3O4@TiO2 heterogeneous photocatalyst for 2-substituted benzimidazoles synthesis under visible light

The method for immobilizing TiO2 nanoparticles on Fe3O4 was presented. On the base of microscopic and spectroscopic characterizations, the prepared Fe3O4@TiO2 nanoparticle composites were employed as a heterogeneous photocatalyst to catalyze the synthesis of 2-substituted benzimidazoles under incandescent light. The composite material exhibited the enhanced photoactivity compared to bare TiO2 and Fe3O4, being able to yield a variety of 2-substituted benzimidazoles in moderate to good yield with recyclability and stability. A possible photocatalysis mechanism was investigated based on the free radical scavengers tracking method. It was evident that holes, ·OH radical and singlet oxygen played the important roles in the synthesis of 2-substituted benzimidazole.

Photoinduced synthesis of 2-substituted benzimidazoles as effective ophthalmology drugs mediated by new heterojunction Fe3O4/ZnO

Benzimidazoles are important medications in ophthalmology primarily due to their ability to treat various eye conditions caused by parasitic infections. Herein, Fe3O4/ZnO is fabricated from the reducing aqueous extract of Petasites hybridus rhizome and introduced as a photocatalyst to synthesize 2-substituted benzimidazoles under illumination of a high-pressure mercury lamp in mild aerobic conditions. The characterization techniques such as SEM, TEM, FT-IR, XPS, UV–VIS, EDS, and XRD are used to identify the photocatalyst. Moreover, various parameters are evaluated on the photocatalytic performance of Fe3O4/ZnO throughout this research. It is realized that the protocol is successful to conduct the condensation reaction across different types of aromatic aldehydes with various substituents. Preliminary mechanistic studies recommended •O2−, OH•, and h+ as reactive oxygen species in the photocatalytic route. Moreover, reusability study confirmed reliable results for the performed photocatalyst for multiple runs, indicating its practical applicability. The successful hot filtration test further validates the stability of the nanophotocatalyst during reactions.

Synthesis and anti-inflammatory activity of benzimidazole derivatives; an in vitro, in vivo and in silico approach

Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.In this context, a series of 2-substituted benzimidazole derivatives was synthesized and assessed for their anti-inflammatory potential through both in vitro and in vivo assays. Molecular docking studies were conducted to elucidate the mechanism of action of these compounds against COX enzymes and other therapeutic targets associated with NSAIDs, such as Aldose reductase, AIKRC, and Phospholipase A2.Among the synthesized compounds, B2, B4, B7, and B8 demonstrated IC50 values lower than the standard ibuprofen, as determined by the Luminol-enhanced chemiluminescence assay. Validation of these findings was achieved through an in vivo carrageenan-induced mice paw edema model, confirming a comparable anti-inflammatory effect to diclofenac sodium observed in vitro. Notably, these compounds exhibited significant binding affinity with all therapeutic targets investigated in this study.These results suggest that the newly synthesized derivatives possess noteworthy anti-inflammatory potential, warranting further exploration for the development of novel multi-targeting inhibitors.

Molecular docking, pharmacokinetic profiling and toxicity studies of 2-substituted benzimidazole derivatives against breast cancer

The most prevalent malignancy among women is breast cancer, which had almost 1.3 million new cases in 2020. It is the second most common cancer in the world, followed by lung cancer. The survival rate would be 99% if the cancerous tumour was limited to the breast. If the cancer migrated to neighbouring lymph nodes, the survival percentage would be 85% and it would drop to 27% if it spread to distant regions. In fact, the most prevalent breast cancer subtype is that caused by excessive estrogen levels. The enhancement of pertinent treatment techniques depends on the estrogen receptors (ER) in both healthy and pathological conditions. There are two primary types of ER, ERα and ERβ, which are each encoded by a different gene. ER status is the most important indicator of breast cancer prediction. To develop novel therapeutics for breast cancer, 30 newly designed benzimidazole compounds targeting the ER were docked. Among them, a compound with a glide score of −9.293 was discovered to be the leading compound. ADME investigations provided additional validation of the docking results. The pyrazole fused benzimidazole nucleus is therefore suggested as a potential pharmacophore for the development of innovative anticancer treatment for breast cancer.

Sodium fluoride-assisted, solvent-controlled regioselective synthesis of 2-substituted and 1,2-disubstituted benzimidazoles with diverse substituents, and unveiling mechanistic insights

The regioselective formation of 2-substituted benzimidazoles and 1,2-disubstituted benzimidazoles with similar substituents at N1 and C2-positions has been achieved by the reaction of o-phenylenediamine derivatives with different aldehydes in the presence of sodium fluoride (NaF) in two different polar solvents. This method is simple, economical, and applicable to a wide range of aldehydes. The method aids in forming 2-substituted benzimidazoles in anhydrous dimethylformamide and 1,2-disubstituted benzimidazoles with similar substituents in glacial acetic acid in excellent yields when using 4.76 mol% of NaF as the catalyst. Furthermore, we have demonstrated the synthesis of 1,2-disubstituted benzimidazoles with dissimilar substitutions at N1 and C2-positions utilizing a one-pot method that eliminates the need to isolate the intermediate 2-substituted benzimidazole. The structure of 1,2-disubstituted benzimidazole (11p) was confirmed using single crystal X-ray diffraction analysis in addition to the spectral studies. These findings emphasize the practical feasibility of our approach to the production of benzimidazole-based drug molecules.

Unlocking the Pharmacological Potential of Benzimidazole Derivatives: A Pathway to Drug Development.

Heterocyclic molecules have fascinated a massive interest in medicinal chemistry. They are heterocyclic compounds that have gained significance due to their diverse variety of pharmacological activities. Benzimidazole is a heterocyclic compound consisting of benzene and imidazole rings. The ease of synthesis and the structural versatility of benzimidazole make it a promising scaffold for drug development. Many biological actions of benzimidazole derivatives have been well documented, including antibacterial, antiviral, anticancer, anti-inflammatory, antitubercular, and anthelmintic properties. The mechanism of action of benzimidazole derivatives varies with their chemical structure and target enzyme. This review has explored numerous methods for producing benzimidazole derivatives as well as a broad range of pharmacological activities. SAR investigations are also discussed in this review as they provide crucial details regarding the essential structural qualities that benzimidazole derivatives must have in order to be biologically active, which could aid in the rational design of new drug candidates. Benzimidazole scaffold is an exclusive structure in drug design and discovery. Many new pharmaceutical drugs containing benzimidazole are anticipated to be available within the next ten years as a result of the extensive therapeutic applications of benzimidazole and its derivatives. This review inspired many researchers to develop more biologically active compounds bearing benzimidazole, expanding the scope of finding a remedy for other diseases. From this study, we concluded that 2-substituted benzimidazole was considered more extensively by researchers.

WO3-ZnO as an anti-gastric cancer agent and efficient photocatalyst in the synthesis of substituted benzimidazoles

Benzimidazoles have potential for developing important drugs and fighting cancerous gastric cells. In this study, an efficient and eco-friendly photocatalyst, WO3-ZnO, is used to synthesize some 2-substituted benzimidazoles by condensing aromatic aldehydes with o-phenylenediamine. The synthesis is achieved by irradiation with a commercial green laser. Various techniques like FT-IR, XRD, DLS, UV–Vis, and FE-SEM are used to analyze structure and properties of WO3-ZnO. The nanocatalyst shows excellent reusability and reproducibility. Additionally, cytotoxicity of WO3-ZnO nanoparticles are tested against KATO-III human gastric cancer cells, and MTT assay confirms their cytotoxicity with a significant reduction in cell viability. The cytotoxicity of WO3-ZnO nanoparticles against the performed cell line under in vivo conditions will be directed soon and the obtained results will be compared with the in vitro conditions.

Water extract of onion: chemoselective synthesis of 2-substituted benzimidazole derivatives

Water extract of onion: chemoselective synthesis of 2-substituted benzimidazole derivatives

Synthesis of 2-Substituted Benzimidazole Derivatives as a Platform for the Development of UV Filters and Radical Scavengers in Sunscreens

The modern trend in sunscreen products is towards the development of UV filters with multi-functional properties, to provide a broad shielding against ultraviolet radiation, antioxidant activity, and the prevention of skin cancer. Additionally, they should also be safe for humans as well as the environment. The benzimidazole heterocycle is a suitable platform for the development of such multifunctional molecules with potential application in cosmetic formulations, due to their ability to act as both UV protectors and reactive pharmacophores. This review presents for the first time the progress in the synthesis and optimization of benzimidazole compounds as UV sunscreen filters. The modifications to the substitution pattern of the lead compound and structure–activity relationships are discussed, as well as the synthetic approaches for the preparation of 2-substituted benzimidazoles. These aggregated data will be useful in future in the development of modern benzimidazole-based sunscreen.

Biological Activities and Chelating Properties of New Benzoyl Derivatives of 2-Substituted Benzimidazoles

Biological Activities and Chelating Properties of New Benzoyl Derivatives of 2-Substituted Benzimidazoles

Synthesis, Characterization and Biological Evaluation of Some Novel N-Mannich Bases of Benzimidazole Derivative

Over the past few decades, Mannich bases of heterocyclic molecules have been grabbing the attention of the synthetic chemists for their wide gamut of biological activities ranging from antibacterial, anticancer, antiparkinson to anticonvulsant, anti-inflammatory, analgesic and anti-HIV. Using the knowledge of important features a novel series was designed to obtain improved antibacterial and antifungal activity. Therefore in the present research, we decided to synthesize 2-substituted benzimidazole derivatives by conventional method. Further the study will extended to introduce sulphanilamide and piperazine group substitution on N-1 position of 2-substituted benzimidazole by Mannich reaction and to screen the newly synthesized compounds for their antibacterial and antifungal activity.

Synthesis, Molecular Docking Studies and Cytotoxic Screening of Novel 2-Substituted Benzimidazole Derivatives

Cancer is one of the most serious lifethreatening diseases for which there is presently no cure. According to current World Health Organization (WHO) reports cancer is responsible for one out of every six deaths worldwide. Benzimidazole is a heterocyclic, aromatic molecule that acts as a biological scaffold with anticancer, antitumor, and antiproliferative activities, among other biological effects. benzimidazole and oxazole are the important pharmacophore in the medicinal chemistry, due to their widespread pharmacological activities. So, to exploit their anticancer potential we have selected these two for our research work. So, in order to develop potential anticancer agents, it was considered of interest to synthesize some benzimidazole derivatives. Before synthesis of molecule, Molecular docking was done and afterwards the compound with lowest dock score selected for synthesis. Synthesized derivatives Characterized By Proton Nuclear Magnetic Resonance (1H NMR), Infra-Red (IR), And Mass Spectroscopy (MS) and screen for cytotoxic activity.

Synchronous Proton-Hydride Transfer by a Pyrazole-Functionalized Protic Mn(I) Complex in Catalytic Alcohol Dehydrogenative Coupling.

A series of Mn(I) complexes Mn(L1)(CO)3Br, Mn(L2)(CO)3Br, Mn(L1)(CO)3(OAc) and Mn(L3)(CO)3Br [L1 = 2-(5-tert-butyl-1H-pyrazol-3-yl)-1,8-naphthyridine, L2 = 2-(5-tert-butyl-1H-pyrazol-3-yl)pyridine, L3 = 2-(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)-1,8-naphthyridine] were synthesized and fully characterized. The acid-base equilibrium between the pyrazole and the pyrazolato forms of Mn(L1)(CO)3Br was studied by 1H NMR and UV-vis spectra. These complexes are screened as catalysts for acceptorless dehydrogenative coupling (ADC) of primary alcohols and aromatic diamines for the synthesis of benzimidazole and quinoline derivatives with the release of H2 and H2O as byproducts. The protic complex Mn(L1)(CO)3Br shows the highest catalytic activity for the synthesis of 2-substituted benzimidazole derivatives with broad substrate scope, whereas a related complex [Mn(L3)(CO)3Br], which is devoid of the proton responsive β-NH unit, shows significantly reduced catalytic efficiency validating the crucial role of the β-NH functionality for the alcohol dehydrogenation reactions. Control experiments, kinetic and deuterated studies, and density functional theory (DFT) calculations reveal a synchronous hydride-proton transfer by the metal-ligand construct in the alcohol dehydrogenation step.