DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology

Abstract

Isoxazole and its derivatives derived from natural resources are very few. However, they have several applications in pharmaceutical industries, including antimicrobial, antitumor, anticancer, antifungal, and antibacterial activities. As a result, this research aimed to design a novel one-pot green approach to synthesize new oxazole derivatives. The derivatives were further explored for their antibacterial and antioxidant activities together with their DFT analysis. Characterization of newly synthesized moieties was done by IR, 1 H NMR, 13 C NMR, CHN analysis, & single-crystal X-ray Crystallography. Further, these compounds were examined for their antibacterial potential by using Gentamycin as a standard drug against S. aureus and E. colibacterial strains. The derivatives 4a, 4c, 4d, 4f, 4j, and 4k possessed excellent antibacterial potential against former, while 4c and 5 showed the highest activity against thelater one.The derivatives were also analyzed for their antioxidant activities by using free radical scavenging (ABTS. & DPPH assays), and Total antioxidant capacity (TAC). Here also, 4a, 4d, 4e, 4k, 4l, 4m, and 5 exhibited the most promising results. Finally, the density functional theory (DFT) analysis was achieved by using the B3LYP methodology with a 6-311+G(d,p) basis set to study the electronic structure of molecules and analysis of chemical reactivity descriptors such as hardness (η), Mulliken electronegativity (χ), chemical potential (μ) and electrophilicity (ω). These properties were calculated from the levels of the predicted frontier molecular orbitals and their energy gap.

Evaluation of Free Radical Scavenging Ability of Triazole-3-Thiol: A Combination of Experimental and Theoretical Approaches

“…Studies suggest that molecules with a lower frontier molecular orbital gap (Δ E L-H ) are more polarized. 41 As presented in Table 1 , AT demonstrates a lower Δ E L-H value (6.29 eV in the gas phase and 6.72 eV in ethanol) compared to AP, indicating higher polarizability and a stronger tendency to react with free radicals. 42 Additionally, hardness (η), a global descriptive parameter directly linked to molecule stability, was computed to provide deeper insights into the reactive nature of the studied derivatives.…”

“…The energy gap between these orbitals, resulting in greater polarizability of the molecule, is typically associated with higher chemical reactivity and lower kinetic stability. Studies suggest that molecules with a lower frontier molecular orbital gap (Δ E L‑H ) are more polarized . As presented in Table , AT demonstrates a lower Δ E L‑H value (6.29 eV in the gas phase and 6.72 eV in ethanol) compared to AP, indicating higher polarizability and a stronger tendency to react with free radicals .…”

Ultra-Sonicated One-Pot Synthesis of Potent Bioactive Biscoumarin and Polycyclic Pyranodichromenone Scaffolds in Aqueous Media: A Complementary Tool to Organic Synthesis

“…The reactivity of molecules and many other significant structural characteristics can be identified through electronic structure calculations. [46][47][48][49] In this study, we have used Gaussian 09W and Gauss view 6.0.16 software to perform the DFT. The B3LYP method and 6-311G(d,p) basis set were used for the DFT calculations.…”

An Efficient Synthesis, Antimicrobial Evaluation and In Silico Studies of 1,2,3‐Triazolyl‐isoxazolyl‐ethanol Derivatives

“…[24][25][26][27] 1,2,3-Triazole-containing compounds received more attention due to their varied biological activities such as antifungal, [28][29][30][31][32][33][34] antimicrobial, [35,36] antivirals, [37,38] antimalarial, [39,40] anticancer [41][42][43] and anti-inflammatory activities. [44,45] The isoxazole containing natural and synthetic compounds reported for a wide range of biological activities such as antimicrobial, [46,47] antibacterial, [48][49][50] antifungal, [51,52] antitubercular, [16,[53][54][55] antiviral, [56,57] anticancer, [58][59][60] and anti-inflammatory. [61][62][63] Some of the FDA-approved and commercialized drugs containing isoxazole and triazole pharmacophore are shown in Figure 1 1) The hybrids of 1,2,4-triazole drugs by clubbing with azole or structural modifications of the fluconazole, isavuconazole, ravuconazole and albaconazole were reported for potential antifungal activity.…”

“…1,2,3‐Triazole‐containing compounds received more attention due to their varied biological activities such as antifungal, [28–34] antimicrobial, [35,36] antivirals, [37,38] antimalarial, [39,40] anticancer [41–43] and anti‐inflammatory activities [44,45] . The isoxazole containing natural and synthetic compounds reported for a wide range of biological activities such as antimicrobial, [46,47] antibacterial, [48–50] antifungal, [51,52] antitubercular, [16,53–55] antiviral, [56,57] anticancer, [58–60] and anti‐inflammatory [61–63] …”