Search

Tioconazole (TCZ), an antifungal medication of the imidazole class has been investigated by experimental FT-IR, FT-Raman, UV–vis and NMR spectroscopy. The optimized molecular geometry and vibrational wave numbers were calculated by DFT/B3LYP/6–311++G(d, p). The detailed vibrational assignments were made by Potential Energy Distribution. The electrophilic and nucleophilic reactive sites were studied using MEP surface. The NBO analysis has been done to describe various hyper-conjugative interactions responsible for the stabilization of the molecule. The 1H NMR chemical shifts were calculated by GIAO method and these matched well with the experimental results, indicating the accuracy of calculation method. TD-DFT calculations have been performed to determine several electronic properties like excitation energies, oscillator strengths, wavelengths and HOMO-LUMO energies. The lipophilicity and aqueous solubility of the compound have been predicted by ALOGPS method. The log P value for TCZ approaches that this compound is less recommended for oral administration. Docking studies have been made to predict the binding orientation, affinity and antifungal activity of the compound. [ABSTRACT FROM AUTHOR]

• Synthesis of a focused library of novel triazolylpyrrolobenzodaizepinone derivatives. • Compound (4l) showed extraordinary in vitro COX–2 inhibition (IC 50 = 18.9 nM)]. • It also showed the best selectivity (COX–1/COX–2 = 1060). • It acted as effective in vivo anti–inflammatory activity without inducing gastric ulceration. • Was found safe in cell toxicity studies on hela cells. • Compound (4l) could act as a potential lead candidate. COX–2, a key enzyme that catalyzes the rate–limiting steps in the conversion of arachidonic acid to prostaglandins, plays a pivotal role in the inflammatory process. Therapeutic utilization of selective COX–2 inhibitors has been considered an effective approach for treating inflammation with emasculated side effects. This study describes the design and enantioselective synthesis of a library of twenty–six novel 1,2,3–triazolylpyrrolobenzodiazepinone derivatives. The molecules were found to exhibit good drug–like properties as implied by the ADMET studies. Nine compounds of the library showing promising results in silico studies were evaluated for cell toxicity on HeLa cells and in vitro COX–1/COX–2 enzyme inhibition. Compounds (2b) and (4l) were found to significantly inhibit COX–2 in vitro in comparison to the standard and compound (4l) with S–geometry showed extraordinary COX–2 inhibition (IC 50 = 18.9 nM) and the best selectivity (COX–1/COX–2 = 1060). (4l) also exhibited the most potent anti–inflammatory activity in vivo in comparison to the standard drugs (Indomethacin and Celecoxib) without inducing any gastric ulceration. Molecular modeling studies aided in the understanding of the interaction modes between this compound and the COX–2 enzyme. Findings in this study may thus serve as a pivotal avenue for developing next–generation selective COX–2 anti–inflammatory drugs using pyrrolobenzodiazepinone (PBD), scaffold. [Display omitted] [ABSTRACT FROM AUTHOR]

• Non-linear optical (NLO) properties of a chalcone-derivative is investigated. • Structure-property relationships of the compound were analyzed. • The sites prone to electrophilic/nucleophilic sites were identified. • The lone pair and anti-bonding orbitals responsible for charge delocalization have been analyzed. • Vibrational contribution to NLO activity was explained in detail. Chalcone derivatives are known for their characteristic non-linear optical efficiency. In the present work, the relation between the molecular structure and non-linear optical properties of a synthesized chalcone derivative 4-[(1 E)-3-(5-chlorothiophen-2-yl)-3-oxoprop-1-en-1-yl] phenyl4-methylbenzene-1-sulfonate (4TPMS) have been investigated by combined experimental and theoretical approaches. The title compound 4TPMS was characterized by spectroscopic techniques viz. Raman, FT-IR, UV-vis, and 1H NMR. Further, the experimental findings were validated by quantum chemical computations. The crystalline geometry of 4TPMS was optimized to energy minima by employing density functional theory (DFT) with B3LYP/6-311++G(d,p) approximation level. Harmonic vibrational frequencies were calculated and the spectral assignments have been done by potential energy distribution (PED) analysis. Significant non-linear optical (NLO) responses of chalcone are mainly caused by charge delocalization between lone pair and antibonding molecular orbitals within the molecule. Hence, natural bond orbital (NBO) was performed to analyze the charge delocalization along with the stability of the molecule. The population analysis based on Charges from Electrostatic Potentials using a Grid based method (CHELPG) was employed to understand the electrophilic/nucleophilic reaction sites. Moreover, the time-dependent density functional theory (TD-DFT) was employed to predict the energies, absorption wavelengths (λ max) and oscillator strengths (f) of the electronic transitions. The TD-DFT calculation successfully reproduces the experimental UV-Vis spectrum of 4TPMS. The chemical shifts observed in 1H-NMR and the calculated GIAO shielding tensors also showed good agreement. A vibrational contribution to the NLO activity and the effect of charge delocalization on the NLO response were illustrated by comparing the similar kind of chalcone derivatives. [ABSTRACT FROM AUTHOR]