Background: Streptococcus mutans and Streptococcus sanguinis are Gram-positive bacteria that cause dental caries. The MurA enzyme is a catalyst in the formation of peptidoglycan in the bacterial cell wall making it ideal as an antibacterial target. Basil (Ocimum americanum) is an edible plant medicine that diverse, very widely spreading, used as herbal for a long time, and it was reported to have pharmacology effect as antibacterial activity. The purpose of this study is to identify antibacterial compounds from O. americanum and analyze their inhibition activity to the MurA enzyme. Methods: Fresh leaves from O. americanum extracted with n-hexane and purified by a combination of column chromatography on normal and reverse phase together with guided by in vitro bioactivity assay against S. mutans ATCC 25175 and S. sanguinis ATCC 10556, respectively, while in silico molecular docking simulation of lauric acid (1) using PyRx 0.8. Results: The structure determination of antibacterial compound by spectroscopic methods resulted in an active compound 1 as lauric acid. The in vitro evaluation of antibacterial activity compound 1 showed the MIC and MBC of 78.13 & 156.3 ppm and 1250 & 2500 ppm against S. sanguinis and in S. mutans, respectively. Further analysis in silico evaluation as MurA Enzyme inhibitor, lauric acid (1) has a binding affinity of -5.2 Kcal/mol those higher than fosfomycin. Conclusion: The lauric acid has potency as a new natural antibacterial agent through the MurA inhibition in bacterial cell wall biosynthesis.

Cyclopurpuracin is a cyclooctapeptide isolated from the methanol extract of Annona purpurea seeds with the following sequence cyclo‐Gly‐Phe‐Ile‐Gly‐Ser‐Pro‐Val‐Pro residue. In this study, a reversed cyclopurpuracin, namely cyclo‐Pro‐Val‐Pro‐Ser‐Gly‐Ile‐Phe‐Gly, was successfully synthesized using a combination of solid and solution phase synthesis methods. The precursor was head‐to‐tail cyclized using 1.25 mM in DCM with 3 eq. HBTU and 1% v/v DIPEA. The final product was obtained (3.8 mg) with an overall yield of 7.4%. The synthetic products were characterized by HR‐ToF‐MS, 1H‐NMR, 13C‐NMR, and 2D NMR, showing different NMR profiles. The presence of the conformation was confirmed by providing additional signals in the 1H NMR and 13C NMR spectrum and the correlation peaks shown by 2D NMR. The presence of the cis conformer in conformer B was proven by the chemical shifts of Ser6 Cβ, Pro7 Cβ, and Pro8 Cβ in conformer B, which were more upfield than the conformer A chemical shifts, and the presence of NOE correlation between Hα/Hα of Val7 and Pro8. The NMR of the reversed cyclopurpuracin revealed the presence of two conformers, conformer A (cyclo‐[trans‐Pro‐Val‐trans‐Pro‐Ser‐Gly‐Ile‐Phe‐Gly]) and conformer B (cyclo‐[cis‐Pro‐Val‐trans‐Pro‐Ser‐Gly‐Ile‐Phe‐Gly]). The presence of dual conformers has not been observed in the NMR spectra of natural cyclopurpuracin.

Xylapeptide B is a cyclopentapeptide isolated from Xylaria sp. derived from the Chinese medicinal plant Sophora tonkinensis. Xylapeptide B was successfully synthesized by a combination of solid‐ and solution‐phase, using the Fmoc strategy, and 2‐chlorotrityl chloride resin. The coupling reagent used is a combination of HBTU/HOBt to assist in the formation of amide bonds. D‐Ala was chosen as the C‐terminal because it has a small residue and can facilitate the cyclization process. Linear peptide was cleaved from the resin using a dilute acid concentration of 20% TFA in DCM because the peptide has no protecting group at the side chain. Crude linear peptide was purified by semi‐preparative RP‐HPLC using 0%–100% ACN eluent for 35 min and obtained a pure mass of 22.4 mg (18.83%). Cyclization was carried out in solution phase using HBTU (3 eq.) and DIPEA (1% v/v) in diluted concentration (1.25 mM) for 72 h at room temperature. The cyclization stage was monitored by thin‐layer chromatography (TLC). Crude xylapeptide B was purified by semi‐preparative RP‐HPLC using 30%–80% ACN eluent for 40 min, to result in 6 mg (8.91%) of the desired xylapeptide B. All synthesized products were characterized by HR‐TOFMS, 1H‐, and 13C‐NMR.

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Background: Streptococcus sanguinis can contribute to tooth demineralization, which can lead to dental caries. Antibiotics used indefinitely to treat dental caries can lead to bacterial resistance. Discovering new antibacterial agents from natural products like Ocimum basilicum will help combat antibiotic resistance. In silico analysis (molecular docking) can help determine the lead compound by studying the molecular interaction between the drug and the target receptor (MurA enzyme and DNA gyrase). It is a potential candidate for antibacterial drug development. Objective: The research objective is to isolate the secondary metabolite of O. basilicum extract that has activity against S. sanguinis through in vitro and in silico analysis. Methods: n-Hexane extract of O. basilicum was purified by combining column chromatography with bioactivity-guided. The in vitro antibacterial activity against S. sanguinis was determined using the disc diffusion and microdilution method, while molecular docking simulation of nevadensin (1) with MurA enzyme and DNA gyrase was performed used PyRx 0.8 program. Results: Nevadensin from O. basilicum was successfully isolated and characterized by spectroscopic methods. This compound showed antibacterial activity against S. sanguinis with MIC and MBC values of 3750 and 15000 μg/mL, respectively. In silico analysis showed that the binding affinity to MurA was -8.5 Kcal/mol, and the binding affinity to DNA gyrase was -6.7 Kcal/mol. The binding of nevadensin-MurA is greater than fosfomycin-MurA. Otherwise, Nevadensin-DNA gyrase has a weaker binding affinity than fluoroquinolone-DNA gyrase and chlorhexidine-DNA gyrase. Conclusion: Nevadensin showed potential as a new natural antibacterial agent by inhibiting the MurA enzyme rather than DNA gyrase.

Background: COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has infected millions of people and caused hundreds of thousands of deaths worldwide. However, until now there has not been found a specific drug for SARS-CoV-2 infection. This prompted many researchers to explore compounds as anti-SARS-CoV-2 candidates. One of the efforts to deal with the spread of the COVID-19 virus is to increase the body's immune system (immune). Medicinal plants known to have the ability as immune-modulators, one of which is Betel leaf (Piper betle L.) those reported to have good activity as antibacterial, antioxidant, anti-viral, and other pharmacological effects. An in silico approach in drug development was used to search for potential antiviral compounds as inhibitors of SARS-CoV-2 Mpro Protein, RBD, and Non-structural Protein (NSP15). Objective:: This study was to determine the potential of Betel leaf compounds as immune-modulators and good inhibitory pathways against COVID-19. Methods: In this study, a potential screening of steroid class compounds, namely 24-propilcholesterol was carried out as an anti-SARS-CoV-2 candidate, using an in silico approach with molecular docking simulations for three receptors that play an important role in COVID-19, namely Mpro SARS-CoV-2, RBD SARS-CoV-2 and non-structural protein (NSP15) and compared with Azithromycin, Favipiravir and Ritonavir as positive control. Results: Based on the results of molecular docking simulations compound from Betel leaf, 24-Propylcholesterol, showed high binding affinity values for spike glycoprotein RBD and non-structural protein 15 (NSP15), namely -7.5 and -7.8 kcal/mol. Meanwhile, a native ligand of Mpro, inhibitor N3, has a higher binding affinity value than 24-propylcholesterol -7.4 kcal/mol. Conclusion: 24-Propylcholesterol compound predicted to have potential as an anti-SARS-CoV-2 compound. However, it is necessary to carry out in vitro and in vivo studies to determine the effectiveness of the compound as an anti-SARS-CoV-2

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Breast cancer is one of the most serious health problems in the world. The common treatments for breast cancer have side effects and resistance, so the search for cancer drugs from natural products that are more effective is still a concern for researchers. Flavonoids from Erythrina crista-galli, which is one of the natural products, have the potential as anticancer drugs based on their phytoestrogen activity that has been reported. The aim of this research is to isolate flavonoids from extract butanol of E. crista-galli with column chromatography and determine their anticancer activity by the in silico molecular docking method. Two flavonoid compounds with the names 6,8-diprenylgenistein from the isoflavone group and phaseolin from the pterocarpan group were isolated. Molecular docking analysis showed that the highest binding affinity values for compounds 1 and 2 were to CDK-2 protein with values of −10.14 and −8.8 kcal/mol, respectively. However, it is also possible to suggest inhibition through ER protein, especially in compound 1, with a value of −10.66 kcal/mol. Therefore, inhibition of the target CDK-2 enzyme is the most promising for the development of new drugs. HIGHLIGHTS Flavonoids have been isolated from butanol extract 6,8-diprenylgenistein and phaseolin were first reported from the species Erythrina crista-galli 6,8-diprenylgenistein has the potential as a new drug candidate with the highest stability based on its ΔG value by targeting the CDK-2 protein within in silico method GRAPHICAL ABSTRACT