The emergence of multidrug-resistant Mycobacterium tuberculosis (MTB) has become a major problem in treating tuberculosis (TB) and shows the need to develop new and efficient drugs for better TB control. This study aimed to use in silico techniques to discover potential inhibitors to the Enoyl-[acyl-carrier-protein] reductase (InhA), which controls mycobacterial cell wall construction. Initially, 391 quercetin analogs present in the KNApSAck_3D database were selected, filters were sequentially applied by docking-based virtual screening. After recategorizing the variables (bond energy prediction and molecular interaction, including hydrogen bond and hydrophobic bond), compounds C00013874, C00006532, and C00013887 were selected as hit ligands. These compounds showed great hydrophobic contributions, and for each hit ligand, 100 ns of molecular dynamic simulations were performed, and the binding free energy was calculated. C00013874 demonstrated the greatest capacity for the InhA enzyme inhibition with ΔGbind = −148.651 kcal/mol compare to NAD (native ligand) presented a ΔGbind = −87.570 kcal/mol. These data are preliminary studies and might be a suitable candidate for further experimental analysis.

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3′, 4′-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-β-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of −7.0, −5.8, −5.2, and −6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of −66.13, −59.36, −40.39, and −40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach.

The SARS-CoV-2 coronavirus outbreak has resulted in severe pneumonia, even death (COVID-19). ADP-Ribose phosphatase (ADPR), a highly conserved macrodomain of this virus, was appropriate for viral RNA replication and transcription. According to studies, quercetin suppresses the main protease and 3-chymotrypsin and papain-like proteases, exhibiting antiviral efficacy against SARS CoV-2. However, quercetin analogs to ADPR have yet to be investigated. This study aims to obtain candidate compounds for ADPR based on binding energy, interaction mode, and binding stability using docking and molecular dynamics (MD) studies.The native ligand (AMP) has estimated binding energy based on docking results of -7.35 kcal/mol. Quercetin analogs, lig_C00013871 (Quercetin 3-(2''-galoylrutinoside), lig_C00006532 ([5',5']-Bisdihydroquercetin), and lig_C00013874 (Quercetin 3-(2G-(E)-p-coumaroylrutinoside) has more negative binding energy, with estimates of -9.43, -9.26, and -8.98 kcal/mol, respectively. These results align with binding energy estimates based on MM-GBSA of -14.76, -29.39, -34.90, and -42.79 kcal/mol for AMP, lig_C00006532, lig_C00013871, and lig_C00013874, respectively. According to the MD simulation, lig_C00006532 and lig_C00013874 will be more effective in stabilizing the ADPR complex. Finally, these two analogs are potential candidate compounds as ADPR inhibitors of SARS CoV-2.

Sansevieria trifasciata Prain holds great potential as a valuable asset in pharmaceutical development. In this study, our focus is to explore and assess the antibacterial activity of various components derived from this plant, including extracts, fractions, subfractions, and isolates, explicitly targeting two common bacteria: Escherichia coli and Streptococcus aureus. The isolated compound, identified as a derivative pyridone alkaloid (5-methyl-11-(2-oxopyridin-1(2H)-yl)undecaneperoxoicacid), demonstrates notable antibacterial effects. The extracts, fractions, subfractions, and isolates reveal significant bacterial growth reductions (p < 0.05). The minimum inhibitory concentration (MIC) values for Escherichia coli were 1.95 ppm, 3.9 ppm, 15.62 ppm, and 7.81 ppm, respectively, while the MIC values for Streptococcus aureus were 1.95 ppm, 1.95 ppm, 15.62 ppm, and 7.81 ppm, respectively. Computational analysis showed the isolates’ interaction with key residues on the active site of β-ketoacyl-ACP synthase from Escherichia coli and TyrRS from Streptococcus aureus. The findings indicate that the isolates exhibit a strong affinity for specific residues, including His333, Cys163, and Phe392 in β-ketoacyl-ACP synthase, as well as Arg88, His117, Glu160, and Gln213 in TyrRS. Comparative energy calculations using MMPBSA demonstrate the isolates’ favorable binding energy (−104,101 kJ/mol for β-ketoacyl-ACP synthase and −81,060 kJ/mol for TyrRS) compared to ciprofloxacin. The elucidated antibacterial activity and molecular interactions of the isolates present valuable knowledge for future in vitro studies, facilitating the development of novel antibacterial agents targeting diverse bacterial strains.

Mycobacterium tuberculosis (MTB) remains the leading cause of infection, with a significant fatality rate, owing primarily to drug resistance. MTB contains the enzyme salicylate synthase, which regulates mycobactin production to bind iron ions from the host cell, facilitating the bacteria to grow and reproduce. This study investigates the potential of marine sponges to inhibit the MTB salicylate synthase by exploiting a computational approach combining molecular docking and dynamics simulations. Forty-six compounds from Xestospongia sp. were chosen from the Marine Natural Products database. The docking results selected four compounds (CMNPD15071, CMNPD7640, CMNPD26706, and CMNPD7639) from this sponge, which provide more negative binding energy than their inhibitors (RVE). After reclassifying their interactions, such as hydrophobic and hydrogen bonds, CMNPD15071 (Sulfuric acid mono-(8-methoxy-12b-methyl-6-oxo-2,3,6,12b-tetrahydro-1H-5-oxa-benzo[k]acephenanthrylen-11-yl) ester) and CMNPD7640 (secoadociaquinone B) performed molecular dynamics simulations to assess their stability. These two compounds show a promising stability profile compared to RVE based on RMSD, RMSF, SASA, and gyration analysis. Furthermore, the binding affinity prediction of these two compounds using the MM/GBSA calculation method reveals that CMNPD15071 (-38.48 kJ/mol) had the highest affinity for binding to MTB salicylate synthase compared to RVE (-35.36 kJ/mol) and CMNPD7640 (-26.03 kJ/mol). These findings demonstrate that compounds from Xestospongia sp. can block MTB mycobactin biosynthesis by inhibiting salicylate synthase.

Scoparia dulcis Linn plays an important role in treatment because it contains active compounds that are proven to have a variety of activities, including cytotoxicity on various cancer cells. The objective of this study is to isolate and identify the cytotoxic compounds in the ethyl acetate fraction of Scoparia dulcis, observe cell cycle inhibition and induction of apoptosis in vitro, and carry out molecular studies using in silico studies. A new diterpene compound was isolated from the ethyl acetate fraction of Scoparia dulcis L. of Indonesian origin. Chromatographic methods were used to isolate the compound, spectroscopic methods were used to elucidate its structure, and these data were compared with those reported in the literature. The compound was tested for its cytotoxic activity against two breast cancer cells (MCF-7 and T47D). The results of the isolated compound showed a cytotoxic effect on MCF-7 and T47D breast cancer cells at IC₅₀ 70.56 ± 1.54 and <3.125 ± 0.43 µg/mL, respectively. The compound inhibited the growth of MCF-7 and T47D breast cancer cells and the accumulation of cells in the G1 phases, and it induced apoptosis. Based on a spectroscopic analysis, the isolated compound was identified as 2α-hydroxyscopadiol, which is a new diterpenoid. A docking study revealed that the isolate’s hydroxyl groups are essential for interacting with crucial residues on the active sites of the ER and PR and caspase-9. The isolate inhibits ER and PR activity with binding energies of −8.2 kcal/mol and −7.3 kcal/mol, respectively. In addition, the isolate was also able to induce apoptosis through the activation of the caspase-9 pathway with an affinity of −9.0 kcal/mol. In conclusion, the isolated compound from S. dulcis demonstrated anticancer activity based on in vitro and in silico studies.