Reactivity and Structural Investigation of Tetrahydroneoprzewaquinone A as an Anti-Inflammatory Agent: An Experimental and Molecular Modeling Perspective

Abstract

This intriguing study aimed to explore the reactivity and structural investigation of (3R,3′R)-2,2′,3,3′-tetrahydroneoprzewaquinone A (THNPQ A) as a potential anti-inflammatory agent. Substantially, the electronic properties were investigated using LanL2DZ, 6-311++G (d,p), and STO-3G basis sets, with electronegativity values of 7.9816, 6.3038, and 5.0166 eV, respectively. The natural bond orbital (NBO) analysis calculations of optimization energies revealed that LanL2DZ had the highest stabilization energy (526.65 kcal/mol) for the interaction between πC8-C9 and πC3-C4. Regarding nonlinear optical (NLO) properties, 6-311++G (d,p) exhibited the highest averaged polarizability and first-order hyperpolarizability values, while the polarizability anisotropies Δtotal followed the order 6-311++G (d,p) (65.2054 a.u.) > LanL2DZ (42.8782 a.u.) > STO-3G (29.9349 a.u.). Analysis of the density of states (DOS) and orbital contribution showed that 6-311++G (d,p) had the highest density peaks at both the highest occupied molecular orbital (HOMO) (–0.5 a.u.) and the lowest unoccupied molecular orbital (LUMO) (0.00 a.u.). The condensed dual descriptors indicated minimal variations in the f A – and f A + values, with an increase in Δf A, f A –, and f A + values following the order STO-3G > LanL2DZ > 6-311++G (d,p). The sites for potential nucleophilic attack were identified as O11, O12, O36, and O37, which exhibited the highest values with the STO-3G basis set. Empirical evidence from in vitro inhibition assays unequivocally validates the potent anti-inflammatory activity of THNPQ A. Particularly noteworthy is its exceptional binding affinity, surpassing that of diclofenac. By establishing conventional hydrogen bonds with the glycine of COX-I and histidine of COX-II, THNPQ A exhibits remarkable potential as an effective agent for combating inflammation. These findings boldly emphasize the promising therapeutic prospects of THNPQ A in the field of anti-inflammatory treatment, positioning it as a compelling candidate for further investigation and development.