Synthesis, spectral, crystal structure, drug‐likeness, in silico, and in vitro biological screening of halogen [Cl, Br] substituted N‐phenylbenzo[g]indazole derivatives as antimicrobial agents

Abstract

The N‐phenylbenzo[g]indazole derivatives, 3‐(4‐chlorophenyl)‐3,3a,4,5‐tetrahydro‐N‐phenylbenzo[g]indazole‐2‐carbothioamide (4CLPBIC), 3‐(4‐bromophenyl)‐3,3a,4,5‐tetrahydro‐N‐phenylbenzo[g]indazole‐2‐carbothioamide (4BRPBIC), and 3‐(3‐bromophenyl)‐3,3a,4,5‐tetrahydro‐N‐phenylbenzo[g]indazole‐2‐carbothioamide (3BRPBIC), were synthesized by the one‐pot green amalgamation of solvent‐free granulating methodology procedure at room temperature. The synthesized crystals were characterized by single‐crystal X‐ray diffraction (SC‐XRD), FT‐IR, FT‐Raman, NMR, and UV–Vis techniques. The molecular geometries from XRD experimental values of synthesized compounds 4CLPBIC, 4BRPBIC, and 3BRPBIC in the ground state are compared theoretically by applying the density functional theory (DFT), a method with the B3LYP/6‐311G(d,p) basis set using Gaussian 09 software. The vibrational assignments of the synthesized compounds were studied based on potential energy distribution (PED) by the VEDA4 program. The scaled DFT/B3LYP/6‐311G(d,p) results show the best agreement with the experimental values. Computational 1H and 13C NMR were acquired by utilizing gauge‐independent atomic orbital (GIAO) procedure, and chemical shift results are in good agreement with the experimental values. A web‐based theoretical investigation was performed to understand the drug‐likeness and ADMET properties of the compounds. Molecular docking studies were carried out against bacterial cholesterol inhibitor block and inhibitor of lanosterol‐14α‐demethylase CYP51 used in the treatment of topical and systemic mycoses in fungal to understand the inhibitory activity of synthesized compounds. The synthesized molecules were also tested for antibacterial and antifungal activities.

Nuclear Magnetic Resonance

“…Dede et al 54 published a similar report on novel naphthoquinone based diimine molecule. Halogen [Cl, Br] substituted N-phenylbenzo[g]indazole derivatives as antimicrobial agents were synthesized and characterized experimentally 55 and the GIAO predicted 1 H and 13 C NMR parameters supported the assignment of their experimental spectra. A novel compound, 4,5-dihydro-9-methoxy-4-(5-methylisoxazol-3yl)benzo[f] [1,4] oxazepin-3(2H)-one, with potential antimicrobial activity, was synthesized and its structural and spectroscopic properties, including DFT calculations of GIAO parameters, were tested.…”

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

“…To predict the binding characteristics of synthetic drugs into the target protein‘s active sites, the sophisticated docking tool Auto Dock Vina was used [62] . To obtain crystal structures of specific proteins, a search was conducted in the Protein Data Bank (http://www.rcsb.org) for the following proteins: crystal structure of hPON1 in complex with 2‐hydroxyquinoline (PDB ID: 3SRG) for antioxidant, [63] Cytochrome P450 14 alpha‐sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with fluconazole (PDB ID: 1EA1) for antifungal, [65] E. coli 24 kDa Domain in Complex with Clorobiocin (PDB ID: 1KZN) for antibacterial, [42] and Auto Dock Tools was employed to analyze the A chain of proteins in pdbqt format, with a focus on enlightening its structure. To ensure accurate results, water molecules that did not participate in any interactions were eliminated, and polar hydrogen atoms were introduced.…”

“…Cytochrome P450 14 alpha‐sterol demethylase (CYP51) is an essential enzyme involved in sterol biosynthesis in eukaryotes and is considered as a promising target for the design of antifungal drugs [64] . The synthesized compounds were docked into CYP51 (PDB ID: 1EA1) [65] and demonstrated antifungal potential. Table 5 presents the results of these simulations, showing that all compounds exhibited binding affinities ranging from −9.5 to 8.7 kcal/mol.…”

1‐Benzyl‐1H‐indazol‐3‐ol Copper(II) Derivatives as Anticancer Agents: In‐vitro Interaction with DNA/BSA, DFT, Molecular Docking and Cytotoxicity on MCF7 Cells

“…Numerous indazole derivatives have demonstrated potent antimicrobial actions against various microorganisms, including bacteria and fungi. [21][22][23][24][25] A few indazole derivatives have been established thoroughly while reflecting significant cytotoxic properties. [26][27][28] Various 2-substituted indazoles derivatives and their metal complexes are known to operate as potential anticancer agents have also been found in several investigations possessing effective cytotoxicity e. g. indazoles compounds possess cytotoxic properties and interfere with DNA topoisomerase I proactively by treating breast cancer (MCF7) impacts.…”

“…Indazole is well known to exhibit variety of biological actions. Numerous indazole derivatives have demonstrated potent antimicrobial actions against various microorganisms, including bacteria and fungi [21–25] . A few indazole derivatives have been established thoroughly while reflecting significant cytotoxic properties [26–28] .…”