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Background: COVID-19, a global pandemic caused by SARS-CoV-2 infection, has led researchers around the world to search for therapeutic agents for treatment of the disease. The main protease (M Pro ) of SARS-CoV-2 is one of the potential targets in the development of new drug compounds for the disease. Some known drugs such as chloroquine and remdesivir have been repurposed for treatment of COVID-19, although the the mechanism of action of these compounds is still unknown. In addition to these known drugs, new drug compounds such as 5-O-benzoylpinostrobin derivatives are also potentially used as SARS-CoV-2 M Pro inhibitors. This study aims to determine the potential of 5-O-benzoylpinostrobin derivatives as SARS-CoV-2 M Pro inhibitors, compared with several other compounds used in COVID-19 therapy. Methods: In silico study was carried out by molecular docking of 5-O-benzoylpinostrobin derivatives using Autodock Vina on two SARS-CoV-2 M Pro receptors with PDB IDs of 5R84 and 6LU7. The free energy of binding was calculated and the the interactions of each ligand were analyzed and compared with reference ligand. Results: Three 5-O-benzoylpinostrobin derivatives each with fluoro, tertiary butyl, and trifluoromethyl substituents at 4-position of benzoyl group showed the lowest free energy of binding value and the highest similarity of ligand-receptor interactions with co-crystalized ligands. These three compounds even exhibited promising results in comparison with other reference ligands such as remdesivir and indinavir. Conclusion:The results of this investigation anticipate that some 5-O-benzoylpinostrobin derivatives have the potential as SARS-CoV-2 M Pro inhibitors.

Drug development is originally carried out on a trial and error basis and it is cost-prohibitive. To minimize the trial and error risks, drug design is needed. One of the compound development processes to get a new drug is by designing a structure modification of the mother compound whose activities are recognized. A substitution of the mother compounds alters the physicochemical properties: lipophilic, electronic and steric properties. In Indonesia, one of medical treatments to cure cancer is through chemotherapy and hydroxyurea. Some derivatives, phenylthiourea, phenylurea, benzoylurea, thiourea and benzoylphenylurea, have been found to be anticancer drug candidates. To predict the activity of the drug compound before it is synthesized, the in-silico test is required. From the test, Rerank Score which is the energy of interaction between the receptor and the ligand molecule is then obtained. Hydroxyurea derivatives were synthesized by modifying Schotten-Baumann’s method by the addition of benzoyl group and its homologs resulted in the increase of lipophilic, electronic and steric properties, and cytotoxic activity. Synthesized compounds were 1-(benzoyloxy)urea and its derivatives. Structure characterization was obtained by the spectrum of UV, IR, H NMR, C NMR and Mass Spectrometer. Anticancer activity was carried out using MTT method on HeLa cells. The Quantitative Structure-Cytotoxic Activity Relationships of 1-(benzoyloxy)urea compound and its derivatives was calculated using SPSS. The chemical structure was described, namely: ClogP, π, σ, RS, CMR and Es; while, the cytotoxic activity was indicated by log (1 / IC50). The results show that the best equation of Quantitative Structure-Cytotoxic Activity Relationships (QSAR) of 1- (benzoyloxy)urea compound and its derivatives is Log 1/IC50 = - 0.205 (+ 0.068) σ – 0.051 (+ 0.022) Es – 1.911 (+ 0.020)

Objectives Bone defect is serious condition that is usually caused by traffic accident. Chitosan is a polymer developed as a scaffold to treat bone defect. However, the mechanism by which chitosan can accelerate bone growth in defect area is still unclear. This study aims to identify proteins which are crucial to the osteogenic properties of chitosan monomer using an in silico study. Methods Molecular docking was carried out on chitosan monomer, which are d-glucosamine and glucosamine 6-phosphate units against bone morphogenetic protein 2 (BMP-2), fibronectin, fibroblast growth factor (Fgf), and phosphate transporter (PiT) using AutoDock Vina. Ligand preparation was carried out using Chem3D version 15.0.0.106, while protein preparation was performed using AutoDockTools version 1.5.6. Results The results showed that glucosamine 6-phosphate had the best binding affinity with fibronectin and PiT, which was −5.7 kcal mol−1 on both proteins, while d-glucosamine had the best binding affinity with PiT (−5.2 kcal mol−1). Conclusions This study suggests that the osteogenic properties of chitosan may be due to the presence of bonds between glucosamine units and fibronectin and/or PiT. However, in vitro studies need to be done to prove this.

In the present work, we have reported the theoretical and biological activities of some imidazole (MIPBD, CMIBP, MIBPBD) derivatives. Here, the synthesis of one novel substituted imidazo-amino pyridinyl derivative (MIPBD) has also been reported. The structure of this compound was identified by NMR and mass spectroscopy. Molecular modeling studies have confirmed that CMIBP (ΔE= 0.16508 eV) is more stable than others. Antibacterial investigation exhibited good to excellent activity for all these compounds against two tested bacterial strains (S. aureus and E. coli). Moreover, molecular docking studies were carried out, which was consistent with experimental studies. The results motivate us for further studies of imidazole derivatives which will be helpful for the development of novel antibacterial agents.

Objective: This research aims to prepare cocrystal of acyclovir (ACV)-nicotinamide (NCT) by solvent evaporation with a variation of solvent (ethanol, glacial acetic acid, and HCl 0.1 N) to improve the bioavailability of ACV as an antiviral drug. Methods:Cocrystal were developed by solvent evaporation with 1:1 molar fraction, using variation of solvent such as ethanol, glacial acetic acid, and HCl 0.1 N. Further, the prepared ACV-NCT cocrystal were characterized for differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and in vitro dissolution.Results: DSC thermogram showed that ACV-NCT cocrystal in ethanol and glacial acetic acid exhibited new endothermic peak at 221.16°C and 216.40°C, whereas no peaks were found for HCl 0.1 N. PXRD diffractogram showed that ACV-NCT cocrystal in ethanol exhibited new diffraction peaks at 2θ 5.9°; 9.2°; dan 13.3°, whereas no peaks were found for glacial acetic acid and HCl 0.1 N. FT-IR characterization of ACV-NCT cocrystal in ethanol showed disappearance of transmission peaks at 3373/cm indicating the loss of NH bands of NCT. Furthermore, C=O of ACV and NCT were observed at 1693/cm, and 1666/cm indicated a formation of hydrogen bonding between ACV and NCT. SEM micrographs showed that cocrystals have a different shape compared to ACV and NCT. DE 15 showed that there was a significant increase of ACV-NCT cocrystal dissolution rate in ethanol compared to the physical mixture and ACV. Conclusion:The study concludes that ACV-NCT cocrystal in ethanol were successfully formed and the dissolution rate of ACV can increase significantly (α=0.05).

Observation of molecular docking results was generally performed by analyzing the docking score and the interacting amino acid residues separately either in tables or graphs. Sometimes it was not easy to rank the tested ligands’ docking results, especially if there were many ligands. This study aims to introduce a new way to analyze docking results with a two‐dimensional graph between the difference in docking score and the similarity of ligand‐receptor interactions. Molecular docking was performed with one reference ligand and several test ligands. The docking score difference was obtained between the test and the reference ligands as the graph’s x‐axis. Meanwhile, the y‐axis contains the similarity of ligand‐receptor interactions, obtained from the ratio of amino acid residues and the types of interactions between the test and reference ligands. Docking result analysis was more straightforward because two critical parameters were presented in one graph. This graph could be used to support the analysis of the docking results.

Background Previous studies have shown that 5-O-benzoylpinostrobin derivatives is a potential anti-breast cancer, with the highest potential being the HER2 inhibitors, is a protein’s member of the epidermal growth factor receptor (EGFR) family. Overexpression of EGFR itself is known to be one of the causes of other cancer, including non-small cell lung cancer (NSCLC). Thus, it is possible that 5-O-benzoylpinostrobin derivatives can also inhibit the overexpression of EGFR in NSCLC. In the case of NSCLC, mutations of EGFR are often found in several amino acids, such as L858R, T790M, and V948R. This study aimed to determine the potential of 5-O-benzoylpinostrobin derivatives as an inhibitor of wild type and L858R/T790M/V948R-mutant EGFR. Methods Docking was performed using AutoDock Vina 1.1.2 on both wild type and L858R/T790M/V948R-mutant EGFR. Parameters observed, consisted of free energy of binding (ΔG) and amino acid interactions of each ligand. Results Docking results showed that all 5-O-benzoylpinostrobin derivatives showed a lower ΔG for both wild type and L858R/T790M/V948R-mutant EGFR, with the lowest ΔG shown by 4-methyl-5-O-benzoylpinostrobin and 4-trifluoromethyl-5-O-benzoylpinostrobin. Both the ligands have the similarity of interacting amino acids compared to reference ligands between 76.47 and 88.24%. Specifically, the ΔG of all test ligands was lower in mutant EGFR than in the wild type, which indicates the potential of the ligand as EGFR inhibitors where a mutation to EGFR occurs. Conclusions These results confirm that 5-O-benzoylpinostrobin derivatives have the potential to inhibit EGFR in both wild type and L858R/T790M/V948R-mutant.