In the present study, a novel quinone-substituted piperazine compound (3) was synthesized and characterized using various spectroscopic techniques including FT-IR,1H NMR,13C NMR, UV-Vis, and MS analyses. The conformational preferences of compound (3) were investigated using the semi-empirical PM3 method, and the lowest-energy conformer was then optimized using the Density Functional Theory (DFT) at the wb97xd/6-311++G(d,p) level to determine its optimized structure. Molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were performed on the optimized structure using the same level of theory. Molecular docking studies revealed that compound (3) binds strongly to DNA and to Escherichia coli DNA gyrase B. Molecular dynamics (MD) simulations over 200 ns indicated that the (3)-DNA and (3)-6F86 complexes remained stable under the simulated conditions. These in silico results provide preliminary insights into the potential biological activities of compound (3), but experimental studies are needed to confirm these findings. The antibacterial and antifungal activities of (3) were evaluated using the disk diffusion method against various Gram-positive and Gram-negative bacterial strains, including Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, and Escherichia coli. The results showed that compound (3) exhibited greater antimicrobial activity than its precursor (1), particularly against Enterococcus faecalis and Micrococcus luteus. Additionally, (3) demonstrated significant antifungal activity against Aspergillus niger and Alternaria alternata.

Thymotrinan is an immunomodulating tripeptide containing the Arg-Lys-Asp sequence.In this study, the structural, vibrational, and electronic properties, as well as the bioactivity of thymotrinan, have been thoroughly examined.The conformational preferences of thymotrinan were evaluated through conformational analysis, and the lowest-energy conformer was then optimized using DFT/WB97XD/6–31 + + G(d, p) theory level.The vibrational wavenumbers of the optimized structure were calculated, and the molecular electrostatic potential (MEP) and frontier molecular orbital (HOMO, LUMO) analyses were performed. To analyze how thymotrinan interacts with the α7 nicotinic acetylcholine receptor chimera and to evaluate its potential to inhibit α-Bungarotoxin, a snake venom protein, molecular docking studies were performed between thymotrinan and target proteins, including the α7nAchR chimera in complex with α-BTx(PDB ID 4HQP), the α7nAchR chimera without the α-BTx protein(α-BTx-removed 4HQP), and α-BTx(PDB code: 1IK8).Afterwards, the thymotrinan-1IK8 complex was subjected to 200 ns of all-atom molecular dynamics (MD) simulations to demonstrate its stability.Based on the MD trajectory, the binding free energy of the complex was estimated to be -18.545 kcal/mol using the MM-PBSA method.In addition, in silico pharmacological predictions suggest that thymotrinan may exhibit anticancer activity against multiple cancer cell lines and antibacterial activity against a range of bacterial species. However, experimental validation of these findings remains required.

Thymocartin, also known as Thymopoietin II (32-35), is a tetrapeptide fragment (Arg-Lys-Asp-Val) of thymopoietin with immunomodulatory properties. In this study, thymocartin was thoroughly examined for its structural features and antibacterial, antiviral, and anticancer activities. Conformational analysis was performed to investigate its conformational preferences and better understand its biological activity. The most stable conformer identified was optimized using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. The vibrational wavenumbers of the optimized structure were calculated and compared with experimental data to evaluate the accuracy of the computational structure. The potential of thymocartin as an anticancer agent was explored through molecular docking simulations with E. coli DNA Gyrase B (PDB ID: 6F86) and the epidermal growth factor receptor (EGFR; PDB ID: 4HJO). Following molecular docking, 200 ns all-atom molecular dynamics (MD) simulations were conducted on the top-scoring ligand-receptor complexes involving 4HJO and 6F86, providing further insight into ligand-receptor interactions. Overall, thymocartin showed diverse biological activities, especially antibacterial and anticancer effects.

Human serum albumin (HSA) is a key transport protein whose ability to bind multiple endogenous and exogenous ligands is governed by site heterogeneity and long-range conformational coupling; however, the mechanisms underlying ligand redistribution among binding sites, particularly in nanoparticulate HSA, remain poorly understood. To address this, we systematically examined the binding of ANS, DAUDA, palmitic acid (PA), and the anticancer lipopeptide PA-EQRPR to monomeric HSA (mHSA) and HSA nanoparticles (HSA-NPs) using steady-state and time-resolved fluorescence spectroscopy complemented by molecular modeling. In mHSA, three spectroscopically distinct binding species were resolved, with fluorescence lifetimes of ∼22.7, 14.5, and 1.6 ns and dissociation constants of 0.33, 9.0, and 3.3 μM, revealing multiple binding environments with distinct affinities and dynamics. Competitive binding experiments demonstrated cooperative PA binding and showed that PA-EQRPR not only displaces ANS or DAUDA but also promotes their redistribution to alternative, more hydrophobic sites, consistent with ligand-induced allosteric site-site communication. Lifetime-resolved analysis of DAUDA further revealed that PA stabilizes long-lived, high-affinity binding states, while PA-EQRPR shifts ligand populations toward deeper hydrophobic environments, enhancing fluorescence. HSA-NPs prepared using ethanol or acetone exhibited markedly different binding behaviors from mHSA, highlighting the impact of protein organization on ligand accessibility. Ethanol-induced HSA-NPs favored long-lifetime, hydrophobic binding species, whereas acetone-induced particles showed reduced site heterogeneity. Docking and molecular dynamics simulations revealed ligand-driven conformational rearrangements that reshape HSA's hydrophobicity landscape. Together, these findings introduce an allosteric population-shift framework that rationalizes multisite ligand binding and redistribution in both monomeric and nanoparticulate HSA.

Two new anthraquinone derivatives: 1-(4-ethylpiperazin-1-yl)-5-chloroanthracene-9,10-dione and 1-(4-methylpiperidine-1-yl)-5-chloroanhtrecene-9,10-dione were synthesized in the laboratory and their structures were confirmed by Fourier transform-infrared and nuclear magnetic resonance techniques. The optimal molecular geometry was determined using a 6-311+G(d,p) basis set and the Density Functional Theory, B3LYP approach. The presence of charge transfer within the molecule was demonstrated by the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). These new anthraquinone derivatives exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria. The highest antimicrobial effect was observed against Gram-positive bacteria, especially Bacillus cereus and Staphylococcus aureus. The antibacterial properties of these new anthraquinone derivatives were also demonstrated by molecular docking simulations using Escherichia coli DNA gyrase B (PDB ID: 6F86). Moreover, molecular dynamics (MD) simulations conducted over a 100 ns period verified that the 1-(4-ethylpiperazin-1-yl)-5-chloroanthracene-9,10-dione-6F86 and 1-(4-methylpiperidine-1-yl)-5-chloroanhtrecene-9,10-dione-6F86 complexes were stable. According to a combination of experimental, computational, and biological research, compounds are promising antibacterial agents that might be developed further.

In this study, the conformational behavior of two dietary dipeptides, H-Trp-Arg-OH (WR) and H‑Trp-Glu-OH (WE), which are agonists of peroxisome proliferator-activated receptor alpha (PPAR-α), was examined using molecular mechanics and molecular dynamics methods. Subsequently, the most stable conformer of each dipeptide, WR and WE, was docked into the PPAR-α ligand-binding domain (PDB ID: 6KB0), DNA (PDB ID: 1BNA), and Human Serum Albumin (HSA; PDB ID: 1AO6) to explore their interaction mechanisms, metabolic roles, and biological activities. The conformational behavior of these dipeptides and the dynamics of their side chains were studied with molecular mechanics, which identified a set of energetically favored conformers. Molecular dynamics studies on the conformational stability of the dipeptides revealed a limited number of stable conformers that tend to adopt unfolded structures. The molecular electrostatic potential (MEP) surface and dipole moment values of the most stable zwitterionic conformation of both dipeptides were calculated at the DFT/B3LYP/6-31++G(d,p) level of theory. Docking studies of WR and WE with DNA (1BNA) showed binding energies of –8.27 and –7.60 kcal/mol, respectively; docking with HSA revealed binding energies of –7.37 and –8.10 kcal/mol, respectively; and docking with 6KB0 showed binding energies of –5.98 and –6.20 kcal/mol, respectively. These docking results clarified the interaction mechanisms between each dipeptide and receptor. Furthermore, the top-scoring WR-6KB0 complex from the docking studies was subjected to 100 ns of all-atom molecular dynamics (MD) simulations to examine the stability of the complex and ligand-receptor interactions in greater detail.

Cancer is still a deadly disease today. The currently employed conventional methods and therapies for cancer treatment are followed by side effects. However, anticancer peptides that can inhibit tumor cell proliferation and migration, or suppress the formation of tumor blood vessels, are less likely to cause drug resistance and have fewer side effects. In this study, the interactions of Glu-Glu-Arg (EER), Glu-Pro-Arg (EPR), and Pro-Arg-Pro (PRP) tripeptides, which have anticancer properties, with human serum albumin (HSA) were evaluated by molecular docking simulations. It was shown that EER, EPR, and PRP tripeptides bind to HSA with favorable binding energies. The PRP tripeptide was the most stable in the HSA receptor among the others, with a binding energy of −8.06 kcal/mol. It was followed by the EPR tripeptide with a binding energy of −7.126 kcal/mol and the EER tripeptide with a binding energy of −6.549 kcal/mol. Human serum albumin is found to be a viable option for the delivery of these tripeptides to cancer cells.

Objective: The antineoplastic agent Pazopanib is effective for treating renal cell cancer and soft tissue sarcoma. The aim of this study was to elucidate the anticancer mechanism of Pazopanib by exploring its molecular interactions with vascular endothelial growth factor receptors (VEGFRs). For this purpose, the most stable structure was determined, and molecular docking and molecular dynamics calculations of Pazopanib with VEGFR1 and VEGFR2 receptors were performed. Materials and Methods: Conformational analysis of Pazopanib was performed using VegaZZ software. Pazopanib was docked to the active sites of the VEGFR1 and VEGR2 receptors (PDB IDs: 3HNG; 3VHE) using Autodock Vina software. The molecular dynamics (MD) simulations were carried out using the YASARA v22.9.24 program with the AMBER14 force field. The anticancer, antibacterial, antifungal, and antiviral activities of the compounds were predicted using PaccMann, AntiBac-Pred, AntiFun-Pred, and AntiVir-Pred. Results: The molecular docking analysis of the Pazopanib molecule with the VEGFR1 and VEGFR2 receptors revealed a strong binding affinity of the investigated molecule towards the targets. The MD simulations, performed for Pazopanib-VEGFR1 and Pazopanib-VEGFR2 complexes showed that each docking complex and intermolecular interactions were stable throughout the simulations. Conclusion: Molecular docking simulations revealed a strong binding affinity of Pazopanib towards VEGFR1 (-8.6 kcal/mol) and VEGFR2 (-9.9 kcal/mol), indicating its efficacy in cancer treatment. During the 40-ns MD simulation of the Pazopanib-3hng and Pazopanib-3vhe complexes, we validated the stability of Pazopanib in the active sites of the receptors. The predicted anticancer, antibacterial, antifungal, and antiviral activities of Pazopanib revealed its versatile bioactivity.

Molecular docking is one of the most widely used techniques for simulating molecular interactions between molecules and forecasting the mode of binding and affinities between them. Due to the presence of structure-function relationship, in this study firstly, the molecular structures of the cellulose I(alpha) and I(beta) molecules were optimized and their most stable structures were determined by density functional theory (DFT) using B3LYP method with 6-31G(d,p) basis set. The vibrational wavenumbers of 1-ring, 2-ring, 3-ring, and 4-ring structures of cellulose I(alpha) and I(beta) were calculated using the same level of theory. Reliable vibrational assignments were made based on potential energy distribution (PED %) of the vibrational modes. The energy gap (Eg = ELUMO-EHOMO) of the cellulose I alpha and cellulose Ip was found to be 8.286 eV and 7.965 eV, respectively. To identify the molecular interactions between cellulose I alpha and Ip ligands and the cellulase enzymes, molecular docking studies were performed. The molecular docking results revealed the strong interaction of the cellulose I alpha and Ip with Endoglucanase enzyme (-6.4 and-6.3 kcal/mol, respectively), enzyme beta-glucosidase (-5.3 and-5.2 kcal/mol, respectively), and Exoglucanase enzyme (-6.1 and-6.2 kcal/mol, respectively).

Bleomycin (BLM) is the first-line clinical antibiotic used in the treatment of cancer. It inhibits DNA metabolism and is used in conjunction with other anticancer medications to treat various kinds of malignant tumors. This work focuses on examining more fully the bioactivity of BLM as both anticancer and antibacterial agents. Due to the structure-function relationship, the conformational study of the molecule was carried out first, and its potential conformations were identified. Afterwards, using the energy minimization feature of the YASARA structure program, the obtained lowest energy conformation of the molecule and the receptor taken from the protein databank (ligand-free) were optimized. BLM was subjected to molecular docking tests with two antibiotic-binding proteins (PDB IDs: 1ewj and 2zw7) to determine its action mechanism as a TN5 transposon inhibitor. Moreover, its binding affinities towards thymidylate kinase (TMK) (PDB ID: 4qgg) Escherichia coli DNA gyrase B (PDB ID: 6f86) were also evaluated to reveal its antibacterial potential. Additionally, ligand-receptor interactions were assessed via molecular dynamics (MD) process to confirm the stability of BLM docked into antibiotic binding protein (1ewj), TMK (4qgg) and E. coli DNA gyrase B (6f86) within 500 ns (for 1ewj and 6f86) or 200 ns of time (for 4qgg). Molecular mechanics/Poisson-Boltzmann Surface Area methods (MM/PBSA) were used to compute the binding energies through MD simulations. Dynamics cross correlation matrices (DCCM) analysis and principal component analysis (PCA) on the MD data were performed. Results have cleared the mechanism of action of BLM having anticancer and antibacterial properties.

To gain deeper insights into the biological activity of thymopentin, its structural, anticancer, antiviral and antimicrobial properties were systematically investigated. Conformational preferences of thymopentin were investigated through conformational analysis and the lowest energy conformation was optimized using density functional theory (DFT) method, Becke three Lee-Yang-Parr (B3LYP) functional and 6-31G(d,p) basis set. Vibrational wavenumbers of the optimized structure were computed and compared with the experimental results. To elucidate the potential of thymopentin as anti-COVID-19 and anticancer agents, molecular docking simulations were performed. Thymopentin was docked into DNA (PDB ID: 1BNA), SARS-CoV-2 main protease (PDB ID: 6M03) and EGFR receptor complex (PDB ID: 4HJO). Additionally, following molecular docking analyses, top-scoring ligand-receptor complexes of thymopentin with SARS-CoV-2 enzyme (6M03) and EGFR (4HJO) were subjected to 50 ns all-atom molecular dynamics (MD) simulations to examine the ligand-receptor interactions in greater detail. Moreover, the antimicrobial potency of thymopentin against the most prevailing human pathogenic microorganisms was also investigated. The strongest antibacterial activity was observed against "Listeria monocytogenes", a pathogenic bacterium capable of causing listeriosis, a serious infection that can potentially lead to death. This study revealed the anticancer, anti-Covid 19 and antimicrobial activities of the thymopentin molecule, demonstrating its multifunctional bioactivity.

SARS-CoV-2 initiates infection by binding its surface spike glycoprotein to the ACE2 receptor on the human cell surface, facilitating the entry of its genetic material into the human cell. Due to the pivotal role of the spike protein in this infection mechanism, in this study the versatility of the bioactivity of the doxylamine molecule was investigated, and by theoretical molecular modeling studies its potential of blocking the entry of the spike protein into human cells was revealed. In the initial phase of this investigation, conformational analysis of doxylamine was executed employing the PM3 method, yielding six stable conformations. Subsequently, the lowest energy conformation obtained was subjected to optimization at the DFT/B3LYP/6-31++G(d,p) level of theory. Vibrational wavenumbers, highest occupied and lowest unoccupied molecular orbitals, and molecular electrostatic potential for the most stable conformer of doxylamine were computed using the DFT/B3LYP/6-31++G(d,p) level of theory. For docking studies firstly, the optimization by energy minimization feature of the YASARA structure program was employed to both ligand and the ligand-free receptor obtained from the protein databank. Molecular docking simulations were adeptly employed to identify potential compounds with doxylamine anticipated to demonstrate inhibitory activity against the spike protein of SARS-CoV-2. Molecular docking study of doxylamine was conducted with spike receptor-binding domain (RBD) of SARS-CoV-2 (PDB ID: 6M0J). Furthermore, ligand-receptor interactions were scrutinized through a molecular dynamics (MD) simulation lasting 125 ns to verify the stability of doxylamine within the ACE2 binding site.

Objective: Short peptides play a significant role in exploring drugs with higher selectivity and fewer side effects in cancer and COVID-19 therapies. This study evaluated the anticancer and anti-COVID-19 activities of Glu-Arg-Gln (ERQ) tripeptide for the first time. To discover the potentiality of the tripeptide as an anticancer and as a SARS-CoV-2 inhibitor, molecular docking analysis of ERQ tripeptide with DNA (PDB ID: 1BNA) and a variety of SARS-CoV-2 enzymes, namely. Main protease (PDB IDs: 6M03, 6LU7) and Spike glycoprotein (PDB ID: 6VXX) were performed.Materials and Methods: To determine the binding efficiency of ERQ to target DNA and proteins, molecular docking processes were carried out using the Autodock Vina program. The sorts of bonds and interacting residues in ERQ/DNA and ERQ/protein complexes were determined.Results: Molecular docking simulations of ERQ tripeptide against 1BNA, 6M03, 6LU7, and 6VXX were performed, and the interactions between the docked ligand and target residues were determined. The binding mechanisms of ERQ with the receptors were clarified. The binding affinities of ERQ towards the targets were predicted to be between -6.3 and -6.7 kcal/mol. ERQ showed the highest binding affinity to Spike glycoprotein (6VXX), with an estimated binding energy of -6.7 kcal/mol.Conclusion: Molecular docking simulations revealed the potential of ERQ tripeptide as an anticancer and anti-COVID-19 agent. High binding affinity against 1BNA (-6.4 kcal/mol), 6M03 (-6.3 kcal/mol), 6LU7 (-6.6 kcal/mol), and 6VXX (-6.7 kcal/mol) indicated that ERQ could be an excellent new natural therapy for the treatment of cancer and COVID-19.

Bioactive peptides have been emerging as drug candidates with increasing importance in the last few decades. In this study, to evaluate the anticancer and antiviral properties of EER (Glu‐Glu‐Arg), EPR (Glu‐Pro‐Arg), and PRP (Pro‐Arg‐Pro) tripeptides, firstly their conformation preferences were searched, and the most stable optimized structure of each tripeptide was determined, using the molecular mechanics force field (MMFF) method and the Spartan06 program. Afterwards, each tripeptide was docked to SARS‐CoV‐2 spike protein receptor‐binding domain (6M0J), SARS‐CoV‐2 main protease (6M03, 6LU7), spike glycoprotein (6VXX), DNA (1BNA), integrins (4WK0, 3ZDX, 1JV2) and epidermal growth factor receptor tyrosine kinase (4HJO). Moreover, molecular dynamics (MD) simulations were performed to validate the stability of the EER, EPR and PRP tripeptides docked to SARS‐CoV‐2 main protease, MPro (6M03) and epidermal growth factor receptor tyrosine kinase (4HJO) within 100 ns time scale and ligand‐receptor interactions were evaluated. The metrics root‐mean‐square deviation, root‐mean‐square fluctuation, intermolecular hydrogen bonding, and radius of gyration revealed that the EER, EPR, and PRP tripeptides form energetically stable complexes with the target proteins. The binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Molecular Mechanics/Poisson‐Boltzmann Surface Area (MM‐PBSA) methods (MM/PB(GB)SA). Principal Component Analysis on MD data was performed to evaluate the energy and structural information of the tripeptide‐protein complexes. Additionally, in‐silico structure‐based pharmacological predictions were made and the anticancer and antibacterial activities of the tripeptides were predicted.

The most stable conformation of molnupiravir (C13H19N3O7), which is frequently used in the COVID-19 treatment, was elucidated by the Spartan06 program. Using the CAVER program, the potential active binding sites that belong to the spike glycoprotein, ACE2 receptor, and both the apo and holo forms of the main protease enzyme(Mpro) of COVID-19 were identified. To determine the binding affinity of molnupiravir to target receptors, molecular docking analyses were carried out using Autodock Vina. The results of molecular docking calculations of the molnupiravir with the spike glycoprotein (PDB ID:6VXX), ACE2 (PDB ID:6M0J;1R42), the apo form (PDB ID: 6M03) and the holo form of COVID-19 Mpro (PDB ID: 6LU7) showed strong binding affinities at -7.8, -7.7, -7.7, -7.1, and -7.4 kcal/mol, respectively. Moreover, top-scoring ligand-receptor complex of the molnupiravir with ACE2 (1R42) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail.

The molecular structure and spectral properties of cyclo(L-Phenylalanyl-L-Proline) dipeptide, which has several biological activities, were investigated. Firstly, conformational preference of the cyclo(L-Phenylalanyl-L-Proline) was searched and obtained lowest energy conformer of the cyclic dipeptide was then optimized using Density Functional Theory with wb97xd/6-311++G(d,p) level of theory. A detailed vibrational spectral analysis has been carried out and assignments of the fundamental modes have been proposed. The experimental vibrational wavenumbers of the investigated compound display good agreement with the computed values. The Frontier Molecular Orbitals, Molecular Electrostatic Potential and electronic transitions of the investigated compound were discussed. In addition, the 1H and 13C NMR chemical shifts of the cyclic dipeptide were calculated and the results were compared with the experimental values. Also, to evaluate the anticancer potential, molecular docking studies of cyclo(L-Phenylalanyl-L-Proline) within the ATP-binding sites of both wild type (EGFRWT; ID: 4HJO) and mutant (EGFRT790M; ID: 3W2O) Epidermal Growth Factor Receptor were performed. The results indicated that cyclo(Phe-Pro) has high binding affinities toward both EGFRWT (-6.6 kcal/mol) and EGFRT790M (-7.7 kcal/mol) receptors, thus, has good anticancer activity and also has potential to overcome drug resistance in therapy. Molecular dynamics simulations on cyclo(L-Phenylalanyl-L-Proline)-wild type complex were conducted through a 50-nanosecond timed to investigate the ligand-receptor interactions in more detail, and to determine the binding free energy accurately. The binding free energy of the cyclo(L-Phenylalanyl-L-Proline)-wild type complex was calculated to be -27.18 kcal/mol.

The detection of intracellular biothiols (cysteine, N-acetyl cysteine, and glutathione) with high selectivity and sensitivity is important to reveal biological functions. In this study, a 2-(2-methoxy-4-methylphenoxy)-3-chloro-5,8-dihydroxynaphthalene-1,4-dione (DDN-O) compound (3) was newly synthesized and used as a fluorogenic probe (detector molecule) in the fluorometric method for the rapid, highly selective, and sensitive determination of biothiols. The intensity values (λex = 260 nm, λem = 620 nm) of the product were measured by adding biothiols to the reaction medium at varying concentrations and the glutathione equivalent thiol content values of each biothiol were calculated. Using compound 3, glutathione as the reference biothiol was detected in the linear concentration range of 10-70 μM and the LOD value was found to be 0.11 μM. Biothiol detection with structurally simple compound 3 was performed at the cellular level within 1 min and the probe was also successfully used in bioimaging with low cytotoxicity. It was concluded that this probe can serve as an alternative to existing fluorescence-based biothiol probes with applications in rapid biothiol detection at the cellular level for biological functions. To evaluate the molecular structure of 3, conformational analysis was performed using the PM3 semiempirical method. The most stable obtained molecular geometry was then optimized at the DFT/wb97xd/6-311++G(d,p) level of theory. Frontier molecular orbitals (HOMO and LUMO) and molecular electrostatic potential map analyses were performed for the optimized structure. Molecular docking studies demonstrated the interactions of 3 with HAS (1AO6) and FhGST (2FHE) target proteins.

Milk derived tripeptides IPP(Ile-Pro-Pro), VPP(Val-Pro-Pro) and LPP(Leu-Pro-Pro) have inhibitory effects on angiotensin converting enzyme, which plays a fundamental role in blood pressure systems. To discover the potentiality of the tripeptides as SARS-CoV-2 inhibitors, molecular docking analyses of IPP, VPP and LPP tripeptides with variety of SARS-CoV-2 enzymes, namely with Main protease, papain-like protease and Spike glycoprotein, were performed. Molecular dynamics simulations were performed to validate the stability of the IPP, LPP and VPP tripeptides docked into SARS-CoV-2 main protease within 50 ns time scale and ligand-receptor interactions were evaluated. Molecular docking and molecular dynamics studies showed that these food-derived tripeptides may be effective against COVID-19.

Amrinone is a class I cardiotonic inotropic agent, which is known to increase the cyclic adenosine monophosphate (cAMP) level by inhibiting the phosphodiesterase 3 (PDE3) enzyme. In this study the theoretically possible stable conformations of the amrinone, was examined first by conformational analysis method and then the obtained most stable conformation was optimized by DFT/wb97xd/6-311++G(d,p) level of theory using Gaussian 03 program. The credibility of the theoretical model was confirmed by comparison of experimental and theoretical vibrational spectra of the title molecule. The fundamental vibrational wavenumbers, IR and Raman intensities of the optimized structure of amrinone were determined using DFT/wb97xd/6-311++G(d,p) level of theory and compared with the experimental vibrational spectra. To investigate the influence of amrinone on cAMP enhancement, the docking simulations towards PDE3B were carried out and the main binding interactions of amrinone with PDE3 were elucidated. Cytochrome P450s (CYPs) are very important phase I metabolizing enzymes. The interaction between amrinone and CYPs (CYP1A2, CYP2C9 and CYP2C19) was investigated by docking simulations. Moreover, molecular docking of the title molecule with different proteins and receptors were studied to reveal potential mechanisms for therapeutic applications. Molecular docking simulations revealed that amrinone showed strong binding affinity to integrins α5β1 (Delta G=-6.6 kcal/mol) and αIIbβ3 (-6.6 kcal/mol), and DNA (-6.5 kcal/mol). The results correlated with its anticancer activity. The drug likeness and ADMET properties of amrinone were analyzed for the prediction of pharmacokinetic profiles. Key words: amrinone, DFT calculations, FTIR, Molecular Docking, ADMET.