Exploration of Indolo[3,2c]isoquinoline derived triazoles as potential antimicrobial and DNA cleavage agents: Synthesis, DFT calculations, and molecular modeling studies

Basavarajaiah, Suliphuldevarada Mathada; Badiger, Jaishree; Yernale, Nagesh Gunavanthrao; Gupta, Nidhi; Karunakar, Prashantha; Sridhar, Bilgumba Thimmaiah; Javeed, Mohammad; Kiran, K.S.; Rakesh, Budimath

doi:10.1016/j.bioorg.2023.106598

Cited by 14 publications

(11 citation statements)

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“…The utilization of MD modeling has emerged as a prominent and indispensable tool in the field of protein-ligand research, enabling scientists to delve into the intricate nuances of protein structural stability and the intricate molecular patterns of interaction [ 42 ]. The conformational sampling of the ligand, protein backbone, and side-chain atoms are achieved through the implementation of a suitably extensive MD simulation [ 43 ]. Contrary to what one might expect, this work of writing provides a deep understanding of the complex dynamics of the solvated system by illuminating the many nonbonded interactions that occur inside it and the consequent energetics.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Thapa,

Biradar,

Nargund

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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Tuberculosis, also known as TB, is a widespread bacterial infection that remains a significant global health issue. This study focuses on conducting a thorough investigation into the synthesis, evaluation of anti-Tb activity, molecular docking, and molecular dynamic simulation of substituted benzimidazole derivatives. A series of twelve substituted benzimidazole derivatives (1–12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FTIR, 1H NMR, and mass spectra. The microplate Alamar blue assay (MABA) was used to evaluate the antimycobacterial activity of the synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/mL) and 8 (MIC = 0.8 g/mL) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard drug (isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of −7.36 and −7.17 kcal/mol, respectively. The simulation results such as the RMSD value, RMSF value, radius of gyration, and hydrogen bond analysis illustrated the optimum potential of compounds 7 and 8 to inhibit the M. tuberculosis strain. Hydrogen bond analysis suggested that compound 7 has greater stability and affinity towards the KasA protein compared to compound 8. Moreover, both compounds (7 and 8) were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Thapa,

Biradar,

Nargund

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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“…[28][29][30][31][32] DMSO served as the negative control, while amoxicillin, penicillin, chloramphenicol, and fluconazole were used as positive controls. [28][29][30][31][32]…”

Section: Minimum Inhibitory Concentration (Mic)mentioning

confidence: 99%

Synthesis and Evaluation of Promising Antibacterial, Antifungal, and Antioxidant Activities for New Imidazo[1,2‐A]Pyridine‐Derived Imines

Moutaouakil,

Roby

et al. 2024

ChemistrySelect

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This study presents the synthesis of a novel series of imine derivatives derived from imidazo[1,2‐a]pyridine as potential therapeutic agents. The imines were obtained by condensing 2‐(4‐bromophenyl)‐6‐chloroimidazo[1,2‐a]pyridine‐3‐carbaldehyde with primary amines, leading to high‐purity products that were characterized using various spectroscopic techniques. The compounds demonstrated promising in vitro antimicrobial activity against various bacteria, including Staphylococcus aureus and Escherichia coli, as well as fungi, such as Candida albicans, Saccharomyces cerevisiae, and Aspergillus brasiliensis. Furthermore, the antioxidant properties of the imine derivatives were evaluated using DPPH and ABTS techniques, and the IC50 values measured revealed their ability to scavenge free radicals. Overall, this study provides a valuable contribution to the field of pharmacology by synthesizing a new series of imine derivatives with significant potential as new therapeutic agents, exhibiting both antimicrobial and antioxidant properties.

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“…In medicine and biotechnology, naphthalimide‐based structures serve as anesthetics, antiviral agents, chemosensors, etc. Moreover, they exhibit antitumor activity in humans [1–3] . The anticancer potential of naphthalimides is attributed to a variety of mechanisms, but it is important to note that specific properties may vary according to the structural features of individual naphthalimide derivatives.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, they exhibit antitumor activity in humans. [1][2][3] The anticancer potential of naphthalimides is attributed to a variety of mechanisms, but it is important to note that specific properties may vary according to the structural features of individual naphthalimide derivatives. Naphthalimides are known to intercalate the DNA double helix.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Aryl‐Functionalized Benzo[d,e]Benzo[4,5]İmidazo[2,1‐a]Isoquinolin‐7‐One Derivatives: DNA Intercalation Causing Cytotoxicity

Türkmen,

Çakır,

Batıkan Kavukcu

et al. 2024

ChemistrySelect

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This study focuses on the cytotoxic effect properties of 4‐aryl‐functionalized benzo[d,e]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one (4‐X−Ar−BBI). The electron‐withdrawing and electron‐donating substituents located at the para position of the phenyl ring attached to the heterocyclic structure have altered the pi electron density within the structure. This change in electron density has influenced the intercalation ability of the heterocyclic structure and has impacted the intensity of its interaction with DNA. The 4‐aryl‐benzo[d,e]benzo[4,5]imidazo[2,1‐a]isoquinolin‐7‐one derivatives (4‐X−Ar−BBI) were prepared via the Suzuki–Miyaura cross‐coupling reaction. The optimum reaction conditions were determined to be 70 °C for 5 hours using catalyst 1 and K2CO3, resulting in a yield of 96 % of 4‐H−Ar−BBI. Characterization of all compounds (4‐X−Ar−BBI) was performed using Fourier Transform Infrared spectroscopy, mass spectrometry, and 1H‐ and 19F‐NMR spectroscopies. The cytotoxic activities of the compounds (4‐X−Ar−BBI) were investigated against cancer cell lines, specifically HeLa (human cervix adenocarcinoma epithelial), PC3 (human prostate), and MCF‐7 (human breast). The stability of 4‐CN−Ar−BBI and the binding modes between 4‐CN−Ar−BBI and DNA were investigated via 1H‐NMR spectroscopy and UV‐Vis spectroscopy, respectively. 4‐CH3−3‐NO2−Ar−BBI exhibited the most potent cytotoxic activity against MCF‐7, and 4‐F−Ar−BBI showed the highest activity against HeLa, with IC50 values of 3.675 and 7.370 μM, respectively.

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Exploration of Indolo[3,2c]isoquinoline derived triazoles as potential antimicrobial and DNA cleavage agents: Synthesis, DFT calculations, and molecular modeling studies

Cited by 14 publications

References 50 publications

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives

Synthesis and Evaluation of Promising Antibacterial, Antifungal, and Antioxidant Activities for New Imidazo[1,2‐A]Pyridine‐Derived Imines

Synthesis of Aryl‐Functionalized Benzo[d,e]Benzo[4,5]İmidazo[2,1‐a]Isoquinolin‐7‐One Derivatives: DNA Intercalation Causing Cytotoxicity

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