BIBECHANA Vol. 22, No. 1, April 2025, 1-14 ISSN 2091-0762 (Print), 2382-5340 (Online) Journal homepage: http://nepjol.info/index.php/BIBECHANA Publisher:Dept. of Phys., Mahendra Morang A. M. Campus (Tribhuvan University)Biratnagar Computational evaluation on spectroscopic (FT-IR, Raman), electronic, biological, and NLO properties of cirsilineol by DFT, ADMET, and molecular docking method Tirth Raj Paneru1,4, Poonam Tandon2, Bhawani Datt Joshi3,∗ 1Department of General Science, Far Western University, Kanchanpur, Nepal 2Department of Physics, University of Lucknow, Lucknow-226007, India 3Department of Physics, Siddhanath Science Campus, Tribhuvan University, Mahendranagar, 10400, Nepal 4Central Department of Physics, Tribhuvan University, Kirtipur, Kathmandu, Nepal ∗Corresponding author. Email: bhawani.joshi@snsc.tu.edu.np Abstract Cirsilineol is a natural product that has pharmacological characteristics and is used to pre- vent the growth of cancer. This study aims to investigate the spectroscopic, electronic, and biological properties of drugs and predict their suitability for drug-like candidates to inhibit prostate cancer. The computational evaluation was performed with density functional the- ory (DFT) at B3LYP/6-311++G(d,p) level of theory and drug-like characteristics rendered from ADMET analysis. Spectral measurement for IR and Raman provided evidence of intra- molecular hydrogen bonding of the OH group in ring R1. The electronic transition properties of the title compound were determined using TD-DFT with a polarized continuum model in solvent ethanol, resulting in a blue shift in absorption wavelength. The electrostatic poten- tial mapped with the van der Wall surface predicted effective electrophiles and nucleophiles, allowing for the layout of intra- and intermolecular hydrogen bonds. The pharmacological properties of cirsilineol determined by ADMED analysis confirmed that it is non-toxic. To assess the biological performance of cirsilineol, molecular docking was performed with protein codes 1E3G and 1GS4, which showed inhibition action with binding affinity -7.7 and -7.8 kcal/mol, respectively. Keywords Cirsilineol, Vibrational spectra, Electrostatic potential, ADMET, van der Waals surface, UV-Vis spectra. Article information Manuscript received: September 25, 2024; Revised: December 7, 2024; Accepted: December 21, 2024 DOI https://doi.org/10.3126/bibechana.v22i1.70126 This work is licensed under the Creative Commons CC BY-NC License. https://creativecommons. org/licenses/by-nc/4.0/ 1 http://nepjol.info/index.php/BIBECHANA bhawani.joshi@snsc.tu.edu.np https://doi.org/10.3126/bibechana.v22i1.70126 https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/ Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 2 1 Introduction Plant-derived products have pharmacological char- acteristics, so they have been used as medications for various types of diseases without harmful effects to the normal cells in body [1]. Flavonoids are pharmacologically significant phytochemical com- pounds found in fruits vegetables, and plant leaves [2]. The plant Artemisia vestita was used in tradi- tional Chinese and Tibetan medicine for joint pain and inflammatory disease, which produces cirsili- neol, also known as 4,5-dihydroxy-3,6,7-trimethoxy- flavone and has antimicrobial, antioxidant, and an- ticancer properties [3, 4]. Research has demon- strated that it possesses anti-tumor properties and reduces the growth of human cancer cells [5]. Ow- ing to its anticancer properties, it has been utilized for treating breast, prostate, and lung cancers, as well as other types of carcinomas, by enhancing the immune system [6,7]. The literature reveals the curative and anti- cancer properties of cirsilineol using experimental and theoretical approaches [6,7]. Paneru et al. con- ducted a theoretical study on the conformational analysis, stability, reactivity, and drug potential of cirsilineol from DFT [8]. Literature indicates that Raman and IR spectra with vibrational anal- ysis, non-linear optical properties as well as elec- tron transition properties based on UV-Vis spec- tra analysis, have not been conducted yet. This study is primarily focused on the investigation of vibrational spectra, electronic transitions, and the more exact prediction of reactive sites in cirsilineol. For this study, quantum chemical calculations were performed on the title molecule using density func- tional theory and the B3LYP hybrid functional with basis set 6-11++G(d, p). This study uses potential energy distribution calculations to conduct a com- prehensive spectroscopic investigation. The electro- static potential was determined by the ESP surface analysis, which provides information about the re- active sites of the molecule. The nonlinear optical (NLO) properties of the title compound were also investigated in terms of dipole moment, polarizabil- ity, and hyperpolarizability to provide insight into its use as an NLO material. The natural charges on each atom were determined by natural popula- tion analysis (NPA). The drug-like properties and toxicity of the molecule were also evaluated by AD- MET analysis. Finally, molecular docking was car- ried out to evaluate the anti-cancer effect of cirsili- neol against protein codes of androgen receptor by detecting binding sites and binding affinity of the title molecule with the target protein codes. 2 Materials and Methods 2.1 Computational details Geometry optimization of the molecule should re- quire to commence the present work, which was accomplished by density functional theory in the Gaussian 09 software package [9, 10]. The com- putations were carried out with the hybrid func- tional B3LYP in the basis set 6-311++G(d,p), the correlation effect, as proposed by Lee, Yang, and Parr, and the exchange interactions, as presented by Becke, are both described by the B3LYP hy- brid functional [11–13]. The electronic transition in orbitals was visualized using GaussView 05 [14] . The confirmation of IR and Raman frequencies, as well as the optimized structure of the molecule, was identified using Chemcraft software [15]. Through the use of harmonic approximation, the IR absorp- tion and Raman intensity of the optimized struc- ture were determined. Multiwfn 8 and VMD 1.9.4 software were used to map the electrostatic poten- tial (ESP) with the molecular van der Wall sur- face [16, 17]. With the polarized continuum model (PCM), the UV-Vis absorption of cirsilineol demon- strating electronic transition on molecular orbital was rendered in gaseous and solvent phases, using the TD-DFT/B3LYP/6-311++G(d,p) level of the- ory [18, 19]. The density of state (DOS) spectrum was produced with the GaussSum 3.0 software, with a full width at half maximum (FWHM) of 0.3 eV [20]. The energy gap in the DOS spectrum was then compared with the energy gap between highest oc- cupied molecular orbital (HOMO) and lowest unoc- cupied molecular orbital (LUMO). To evaluate the ADMET properties of cirsilineol, the Swiss ADME and PKCSM online web tool was used [21,22]. Auto Dock Tools (ADT) version 1.5.4 has carried out the molecular docking of the molecule [23]. Finally, the binding positions of the title molecule with the PDB codes of the androgen receptor were displayed using Discovery Studio Visualizer 4.5 [24]. 3 Results and Discussion 3.1 Geometry optimization The compound cirsilineol (CID 162464) was down- loaded from the PubChem database, [25] and optimized using density functional theory with the B3LYP/6-311++G(d,p) level of theory. The ground state energy of cirsilineol was found to be -767078.745 kcal/mol, which is identical to the en- ergy (-767080.126 kcal/mol) for the most stable conformer of cirsilineol as evaluated by Paneru et al. using the same level of theory [8]. The op- timized structure of cirsilineol with a numbering scheme on the atoms is shown in Fig. 1. The op- timized structure was used for further study of the Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 3 title compound. 3.2 Vibrational Assignment The use of vibrational spectroscopy, such as Fourier-transform infrared (FT-IR) and Raman, can generate important insights into the interac- tions and structure of molecules. Cirsilineol consists of 41 atoms with (3N-6) 117 modes of vibration, all of those being IR and Raman active. The spec- tral wavenumbers for IR and Raman were calcu- lated at the B3LYP/6-311++G(d,p) level of theory, but they were overestimated due to anharmonic- ity, so they were reduced using the wavenumber linear scaling (WLS) factor [26]. The vibrational wavenumber calculations and potential energy dis- tribution assignment were performed in Gar2ped in accordance with Pulay's recommendations [27, 28]. The Raman intensity was not directly obtained from DFT calculations it can be obtained from the Raman scattering cross-section. Raman scattering cross-section is proportional to the amplitude and provided by the following relation [29]. ∂σj ∂Ω = ( 24π4 45 ) (ν0 − νj) 4 1− exp [ hcνj kT ] ( h 8π2cνj ) Sj where, h, c, and k as a universal constant. Sj and νj be the scattering activity and predicted wavenumber of jth mode , and ν0 be the wavenum- ber related to the excited state. Simulated spec- tra are produced by convoluting each predicted vi- brational mode with the computed Raman and IR intensities using a Lorentzian line shape with a full width at half maximum (FWHM) of 8 cm-1 [30]. Table 1 displays both the unscaled and scaled wavenumbers for FT-IR and FT-Raman, as well as their PED distribution. The graph of IR ab- sorbance plotted against the scaled wavenumber, adjusted using the WLS factor derived from DFT calculations, is presented in Fig. 2. The graph for the Raman spectra obtained by plotting the graph between Raman intensity and scaled wave number is shown in Fig. 3. Using the potential energy dis- tribution in Table 1, and the IR and Raman spectra shown in Figures 2 and 3, we illustrated the vibra- tional modes associated with the functional groups, rings, and methyl groups of cirsilineol in the follow- ing sections. 3.2.1 O-H Vibrations Cirsilineol has two OH groups on rings R1 and R3. This group may be reactive parts of molecules, al- lowing it to participate in intra- and intermolecular hydrogen bonds. The stretching vibration of the free O-H group in ring R3 is 3624 cm-1, while the stretching vibration of the O-H group in ring R1 is 3064 cm-1. The stretching vibration of free OH in a similar type of flavonoid, such as kaempferol, was computed to be 3626 cm-1; in quercetin, 3640, 3598 cm-1; in myricetin, computed to be 3546, 3608 cm-1; and in catechol, computed to be 3647 cm-1 us- ing B3LYP/6-31+G(d,p) level of theory. These are in agreement with our result [31]. The stretching vibration of the O-H group in ring R1 was found to be lower, confirming the presence of O4-H31. . . O5 intra-molecular hydrogen bonding. The O-H vibra- tion of rings R1 and R3 showed a sharp peak in both IR and Raman spectra, whereas the vibration of O-H in ring R1 shifted to the lower frequency in IR and Raman spectra. The deformation of O-H groups occurred at 1415 and 1195 cm-1. 3.2.2 O-CH3 Vibrations There are three methyl moieties in cirsilineol, and each one can vibrate in the different ways, includ- ing stretching, deforming, and rocking. The methyl group exhibits asymmetric stretching in the range of 2970-2950 cm-1 and symmetric stretching in the range of 2880-2860 cm-1. Asymmetric deformations should fall within 1470-1430 cm-1, while symmetric deformations should be within 1380-1370 cm-1 [32]. Asymmetric stretching of the methyl group was computed to be 3009, 3006, 3002, and 2941 cm-1, whereas symmetric stretching was obtained at 2977, 2972, 2900, 2899, and 2886 cm-1. The asymmetric deformations of the methyl group were calculated at 1489, 1486, 1480, 1470, 1465, and 1464 cm-1, while the symmetric deformations were determined at 1459, 1458, and 1447 cm-1. Methyl moieties were found to be rocking at 1203, 1195, 1188, 1156, and 1155 cm-1. These observations have shown that the calculated wavenumbers for various vibrations falls within the range reported in the literature. Figure 1: Optimized structure of cirsilineol showing intra-molecular hydrogen bonding (O- H. . . O) and numbering scheme on atoms. Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 4 Figure 2: Calculated IR spectra of cirsilineol at the B3LYP/6-311++G(d,p) level of theory. Figure 3: Calculated Raman spectra of cirsilineol at the B3LYP/6-311++G(d,p) level of theory. 3.2.3 Vibrations in ring R1 Ring R1 consists of one C-H moiety and three C-O moieties. The Stretching, in-plane bending, and out-of-plane bending should all be in the range 3100-3000 cm-1, 1350-950 cm-1, and 1100-600 cm-1, respectively [33]. Stretching of C- H was calculated to be 3076 cm-1, with in-plane bending at 1170 cm-1 and out-of-plane bending at 835 cm-1. C-C stretching in ring R1 occurred at 1651, 1617, 1566, 1697, 1632, 1364 and 1303 cm-1. C-O stretching was obtained at 1224 cm-1 with a 22% PED contribution, whereas other C-O stretch- ing had a lower PED contribution. Because the CH3 group is attached to the C-O group, the in- plane and out-of-plane bending contributes signif- icantly less in PED. The ring showed trigonal de- formation at 712 cm-1 and asymmetric deformation at 576 cm-1, with a lower contribution from PED. Additionally, the ring showed puckering and torsion at 768 and 629 cm-1. Their contribution with the peak observed in IR and Raman spectra. 3.2.4 Vibrations in ring R2 Ring R2 contains one C-H moiety and one C=O group. The stretching vibration of C-H was ob- tained at 3076 cm-1 with in-plane deformations and out-of-plane deformations computed at 1281, 1272 cm-1, and 850, 844 cm-1 respectively. The in-plane bending of C-H is a lower PED contribution. The stretching of CO occurred at 1605 and 1586 cm-1 with PED contributions of 21% and 15%, respec- tively; the lower PED contribution of the CO group is due to its participation in hydrogen bonding with the O-H group of ring R1. The stretching vibra- tion of C=O aligns with those of myricetin at 1603 and 1570 cm-1, as well as with quercetin at 1604 and 1571 cm-1 [31]. C-C stretching in ring R2 was calculated at 1586 and 1281 cm-1. The asymmetric torsion, trigonal deformation, asymmetric deforma- tion, and ring puckering occurred at 693, 524, 891, and 738 cm-1, respectively, but had a lower PED contribution. 3.2.5 Vibration in Ring R3 In ring R3, there are three C-H groups with two C- O groups attached to hydrogen and methyl groups. The C-H stretching wavenumber were obtained at 3092, 3064, and 3022 cm-1, while the in-plane bend- ing was computed at 1529 and 1178 cm-1, and the out of plane bending were occurred at 925 and 812 cm-1. The stretching of C-O was computed at 1529, 1303, and 1272 cm-1, while its in-plane bending and out-of-plane bending were computed at 560 and 467 cm-1, respectively, with lower contribution in PED. The C-C stretching in the ring was determined at 1605, 1604, 1426, 1415, 1374, and 1293 cm-1. The trigonal and asymmetric deformations in the ring occurred at 1272, 1052 cm-1 and 675, 642, 536, and 524 cm-1, respectively. The puckering and asym- metric torsion values were calculated at 878, 741, 738, and 583 cm-1 and 812, 583, 467, and 449 cm-1, respectively. Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 5 Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 6 Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 7 3.3 Density of states (DOS) When an electron transitions from the valence band to the conduction band, it results in a definitive change in the density of states [34]. The density of state spectra produced in the GaussSum 3.0 soft- ware with a full width at half maximum (FWHM) of 0.3 eV. The DOS spectrum for cirsilineol in the gaseous and solvent phase ethanol is shown in Fig. 3. Bonding interaction is suggested by a positive value on the DOS spectrum, anti-bonding is indi- cated by a negative value, and no bonding is in- dicated by a zero value. The green lines in the spectrum represent the highest occupied molecular orbital (HOMO), while the red lines represent the lowest unoccupied molecular orbital (LUMO). Ac- ceptor orbitals are represented by virtual orbitals, and donor orbitals are represented by occupied or- bitals. The high intensity of DOS represent mul- tiple state of occupation at that energy level [35]. It was found that the energy gap in the DOS spec- trum and the HOMO-LUMO gap in cirsilineol were identical. Cirsilineol is more reactive in the ethanol solvent and stable in the gaseous medium because the energy gap in the solvent phase was found to be less than that of the gaseous phase. 3.4 UV-V is spectrum and electronic tran- sition UV-Vis spectroscopy is the most fundamental tool for analyzing the absorption properties of pharma- cological molecules, allowing us to better compre- hend intra- and intermolecular interactions [36]. In this study, the UV-Vis spectrum was plotted in gaseous and solvent phase ethanol using TD-DFT in the IEF-PCM model to analyze the electronic transition between HOMO and LUMO [37]. Table 2 presents the major electron transitions along with their corresponding excitation energies, absorption wavelengths, and oscillator strengths. Fig. 4 dis- plays the UV-Vis absorption spectra of cirsilineol in gaseous medium and solvent (water, ethanol, and methanol). The transition from HOMO→LUMO is the first excited state has an absorption wavelength of 363.40 nm with excitation energy of 3.41 eV in a gaseous medium and an absorption wavelength of 359.80 nm with excitation energy of 3.44 eV in sol- vent ethanol. The absorption in solvents shifted to a shorter wavelength is a blue shift, because the po- larity of solvent increases. The decreases in absorp- tion wavelength in solvent ethanol are due to the transition from n→π∗ [38]. Figure 5 depicts the significant transition between HOMO and LUMO of cirsilineol in gaseous and solvent ethanol. The solvent facilitates charge transfer more readily than a gaseous medium; hence, the band gap in a solvent decreases, which increases its reactivity. Figure 3a:Density of states spectrum of cirsilineol in (a) gaseous and (b) solvent (EtOH) phases. Figure 4: The UV-Vis absorption spectrum of cir- silineol (in gas and solvent phases). Figure 5: Major transition between HOMO and LUMO in gaseous and solvent EtOH phases. Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 8 3.5 Electrostatic potential (ESP) surface analysis The foundation for the biological activity of a drug molecule can be laid by understanding the inter- molecular interactions in molecules through the use of the electrostatic potential surface [39]. ESP dis- played to the surface extrema of cirsilineol is shown in Fig. 6. The points of minimal and highest ESP were indicated in the figure by the blue and or- ange spots [40]. The regions of positive and nega- tive potential on the molecule's surface were repre- sented by the colors blue and red, respectively. The global minimum potential of the molecule was de- termined to be -38.38 kcal/mol, which is attributed to O5. The global maximum potential was found to be 56.88 kcal/mol, corresponding to H38. The largest positive potential on H38 is due to its at- tachment to oxygen, which attracts a large number of electrons from H38. This shows that the most effective electrophile and nucleophile for participat- ing in intermolecular interactions are H38 and O5, respectively. The intermolecular hydrogen bonding formed by intermolecular interaction H38. . . O5 can form the crystal-packing of cirsilineol. All hydro- gens in the molecule have positive potential, while oxygen has negative potential. 3.6 Natural population analysis Mullikens charges are highly sensitive to the choice of basis sets; hence, natural population analysis is an alternative to it, which better describes the electron distribution in the compounds [41]. The natural population analysis determines the natural atomic orbitals and their occupancies and provides a natural atomic charge on each atom [42]. The natural charges on each atom of cirsilineol calcu- lated at B3LYP/6-311++G(d,p) level of theory are presented in Table 3. The graph plotted between natural charges and each atom of the cirsilineol is also shown in Fig. 7. All the hydrogen atoms have positive charges, with H31 being the most electron- deficient and exhibiting the highest positive charge. Therefore, H31 is the most favorable site for nucle- ophilic attack. Conversely, all the oxygen atoms have negative charges, with O4 and O5 displaying the highest negative charges and possessing excess electrons. Consequently, O4 and O5 are potential sites for electrophilic attack. Due to this conse- quence the intra-molecular hydrogen bonding O4- H31. . . O5 was formed. C16, which has the high- est negative charge of -0.3396 e, behaves as a nu- cleophile, while C12 exhibits the highest positive charge of 0.4840 e and acts as an electrophile. Figure 6: ESP mapped molecular vdW surface of cirsilineol. Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 9 Figure 7: Distribution of natural charges calculated from natural population analysis. 3.7 Nonlinear optical (NLO) properties When the electromagnetic field interact with the molecule it will causes formation of new field, change in phase, amplitude, frequency and other propagation properties of incident field which re- lated with the nonlinear optical properties [43]. It gives key information in frequency shifting, op- tical communication, switching, data storage as well as signal processing [44]. The calculation of static dipole moment µ0, mean polarizability |α0| , anisotropy of polarizability (∆α), and first order hyperpolarizability β0 of the most stable conformer of title molecule has been carried by us- ing DFT at B3LYP/6-311++G(d,p) level of theory from the relations [45]: µ0 = ( µ2 x + µ2 y +µ2 z ) 1 2 |α0| = 1 3 (αxx + αyy + αzz) ∆α = 2− 1 2 [ (αxx − αyy) 2 + (αyy − αzz) 2 + (αzz − αxx) 2 + 6α2 xx ] 1 2 β0 = [ (βxxx + βxyy + βxzz) 2 + (βyyy + βxxy + βyzz) 2 +(βzzz + βxxz + βyyz) 2 ] 1 2 The components of static dipole moment, first order hyperpolarizability, mean polarizability and anisotropy of cirsilineol molecule are shown in Ta- ble 4. From the table it was found that cirsilineol have static dipole moment µ0 was found to be 4.009 Debye, first order hyperpolarizability β0 found to be (16.173×10-30 esu), and anisotropy of polarizability was found to be (107.698×10-24 esu). These values are larger than that of urea, hence it encourages the title molecule can be considered as an excellent NLO material [46]. 3.8 ADMET properties analysis Most pharmaceuticals in clinical trials fail to reach the market due to their limited potential and side effects, making the development of new medications difficult. ADMET analysis evaluates the absorp- tion, distribution, metabolism, excretion, and tox- icity of drug molecules [47]. The SwissAdme tool determined that cirsilineol has a molecular weight of 344.32, with four rotatable bonds, seven H-bond acceptors and 2 donors, 142.160 Å2 topological po- lar surface areas (TPSA), and 91.44 molar refrac- tivity. The bioavailability score and lipophilicity were found to be 0.55 and 2.53 respectively. All of these physicochemical parameters fall within the range of Lipinsky rules for drug likeness; hence cir- silineol can be used as an antimicrobial drug [48]. The solubility, TPSA, flexibility, molecular weight and lipophilicity except saturation of the title com- pound lie within the pink region of the radar plot given in Fig. 8 (a) indicating that cirsilineol is ex- cellent in terms of bioavailability. The diagram of the boiled egg model in Fig. 8 (b) indicates that the red dots are located within the white region, suggesting that cirsilineol is effectively absorbed in the gastrointestinal tract and enhances bioavailabil- ity [49]. The pharmacokinetic properties determined by the online tool PKCSM as well as the ADMET properties for the title compound in terms of suit- ability for human administration are presented in Table 5. Cirsilineol has 100% intestinal absorption and a solubility of -3.326 mol/l, which is higher than Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 10 -4 mol/l. Additionally, it has a skin permeability of -2.75 cm/h, indicating desirable pharmacologic properties for absorption and distribution [50]. If the volume of distribution (VDs) is high, the drug will be distributed in plasma rather than tissue, which is in the desirable range for the title com- pound. BBB and CNS permeability were deter- mined to be 0.738 (log BB) and -3.116 (log PS), re- spectively, indicating that they were unable to cross the blood-brain barrier and central nervous system. Additionally, it has a good metabolism and excre- tion, with a clearance of 0.638 (ml/min/kg). It is not positive to toxicity of AMES, indicating that it is mot mutagenic. The anticipated maximum dose for humans to be tolerated was 0.275 (mg/kg/day), which suggests a moderate level of tolerance. Fi- nally, the fact that it responds negatively to enzyme inhibitory capacity, hepatotoxicity, and skin sensi- tivity suggests that it is not harmful. Hence, each of these qualities supported the medicinal nature of cirsilineol. 3.9 Molecular Docking Molecular docking is a computational technique used to understand how drug molecules bind with the target receptor with the preferred orientation and find the binding affinity between them [51]. It has been reported that cirsilineol shows anti- cancer effects against human cancer cells, includ- ing prostate cancer. Literature has reported that androgen receptors have been associated with the progression of prostate cancer and are known to play a crucial role in male reproduction [52, 53]. cirsilineol inhibits the development of prostate can- cer cells through the stimulation of ROS-mediated apoptosis [7]. In this study, we performed molec- ular docking with androgen receptor protein codes 1GS4 and 1E3G, which were downloaded from the protein data bank [54]. The water was taken out of the protein and Kollmann's charge was added in order to identify the active sites of the protein for a grid box of 60Åx60Åx60Å with a spacing of 0.375 Å. Figure 9 displays the binding modes illustrating the various interactions between cirsilineol and the pro- tein codes 1E3G and 1GS4. For the protein codes 1E3G and 1GS4, the binding affinity and various docking evaluation parameters are shown in Table 6. The active binding sites of protein codes 1E3G and 1GS4 both are confirmed at the centre hav- ing coordinates x = 6.786, y = 27.710 and z = 11.102. The binding affinity with 1E3G and 1GS4 were found to be -7.7 and -7.8 kcal/mol respectively. The inhibition constant for 1GS4 was found to be less as compared to 1E3G and RMSD between the initial structure and docked structure is 0.58 Å for 1GS4 hence title compound is a potential inhibitor of 1GS4. Figure 8: (a) Boiled-egg permeation plot and (b) Bioavailability radar plot of cirsilineol. Figure 9: Docking of different protein codes of an- drogen receptor with cirsilineol showing best binding modes and interactions Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 11 4 Conclusion In this study, we employed DFT calculations to ana- lyze the vibrational bands (FT-IR and Raman) as- sociated with various moieties of cirsilineol. The FT-IR and Raman spectra were simulated, and the stretching vibrational wavenumber of the OH group in ring R1 was found to be lower due to the ex- istence of intra-molecular hydrogen bonding O4- H31. . . O5. The DOS spectrum indicates an elec- tron transition from the valence band to the con- duction band, suggesting that the band gap in the ethanol solvent is 3.92 eV, while in the gaseous medium it is 3.97 eV. This suggests that the ti- tle compound is more reactive in an ethanol sol- vent. The transition of electrons between HOMO and LUMO is the first excited state for both gaseous and solvent mediums, with absorption wavelengths of 363.40 nm and 359.80 nm, respectively. The de- crease in wavelength in the solvent indicates a blue shift, and there is a transition from n→*. The elec- trostatic potential mapped with the van der Waals surface showed that the global minimum and max- imum potential of cirsilineol were determined to be -38.38 kcal/mol for O5 and 56.88 kcal/mol for H38, respectively. This implies that O5 and H38 Tirth Raj Paneru et al./ BIBECHANA 22 (2025) 1-14 12 are the effective nucleophile and electrophile, which could lay the groundwork for intermolecular hydro- gen bonding in crystal packing. Natural population analysis predicted that O4 and H31 atoms had the highest negative and positive charge, respectively, supported the intra-molecular hydrogen bonding O4-H31. . . O5. The NLO study confirmed that cir- silineol can be used as an NLO material. ADMET analysis confirmed that the title compound is non- toxic and orally accepted. Finally, molecular dock- ing with the androgen receptor shows that it has the lowest binding affinity of -7.8 kcal/mol with the pro- tein code 1GS4 and the lowest inhibition constant, suggesting that cirsilineol may be an inhibitor of 1GS4. Acknowledgments T.R. Paneru acknowledges DST, India for granting a partial fellowship (INSA/DST- ISRF/2023/NEP/08/13), and B.D. Joshi acknowl- edges the University Grant Commission (UGC), Nepal for partial financial support to this work under the Faculty Research Grant (FRG-79/80- S&T-05). Author Contributions T.R. Paneru: Writing-original draft, investigation, and Formal analysis; P. Tandon: Software and su- pervision; B.D. Joshi: Writing-review, editing, and supervision. Data Availability The data supporting the findings of this study are available from the corresponding author upon rea- sonable request. References [1] D.K. Patel. Health benefits, therapeutic ap- plications, and recent advances of cirsilineol in the medicine: Potential bioactive natu- ral flavonoids of genus artemisia. EMIDDT, 23:894–907, 2023. [2] A. Ullah, S. Munir, S.L. Badshah, N. Khan, L. Ghani, B.G. Poulson, A. H. Emwas, and M. Jaremko. Important flavonoids and their role as a therapeutic agent. Molecules, 25:5243, 2020. [3] G.O. Kim, J.B. Heo, D.H. Park, G.Y. Song, and J. S. Bae. 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Bourne. The rcsb protein data bank: redesigned web site and web ser- vices. Nucleic Acids Research, 39:D392–D401, 2011. Introduction Materials and Methods Computational details Results and Discussion Geometry optimization Vibrational Assignment O-H Vibrations O-CH3 Vibrations Vibrations in ring R1 Vibrations in ring R2 Vibration in Ring R3 Density of states (DOS) UV-V is spectrum and electronic transition Electrostatic potential (ESP) surface analysis Natural population analysis Nonlinear optical (NLO) properties ADMET properties analysis Molecular Docking Conclusion