Research in Pharmaceutical Sciences

Background and purpose: Pyrrosia longifolia is one of the medicinal plants in Indonesia. However, it has received little attention regarding pharmacological properties and phytochemicals. This study aimed to isolate bioactive compounds and evaluate their antibacterial activities. Experimental approach: The secondary metabolites were isolated using a bioassay-guided approach. The aerial part was macerated in methanol and the crude methanol was partitioned with organic solvents to obtain n-hexane, dichloromethane, ethyl acetate, and water extracts. The ethyl acetate extract was purified using chromatography procedures, yielding six chemicals, and their structures were determined using spectroscopy. The antibacterial activity of the compounds was evaluated. Findings/Results: Six secondary phytochemical metabolites were identified including naringin (1) , catechin (2) , quercetin (3) , rutin (4) , kaempferol (5) , and mangiferin (6) . The absolute configurations of compounds 1 and 2 were ascertained using electronic circular dichroism as 2S for naringin and 2R, 3S for catechin. The compounds exhibited antibacterial activity against several pathogenic bacteria, with MIC and MBC values ranging from 7.8 to 250 μg/mL. Computational investigations of these compounds revealed a substantial affinity for bacterial receptors’ active and allosteric regions. Furthermore, rutin exhibited the capacity to reduce the activity of β-ketoacyl-acyl carrier protein synthase III, enhancing its antibacterial effectiveness. Conclusion and implications: The in-vitro assessment revealed that the six identified compounds possess a wide range of antibacterial activity, which was corroborated by in-silico analyses. However, further investigation is required to back up the conclusion of this study.

Hilwan Yuda Teruna

Rohimatul Khodijah

Neni Frimayanti

Rudi Hendra

Phytochemicals from Pyrrosia longifolia (Burm. f.) C.V. Morton with antibacterial activity

来自石韦（Pyrrosia longifolia (Burm. f.) C.V. Morton）的植物化学成分及其抗菌活性

Background and purpose: Lapatinib (FMM) and 5-fluorouracil (5-FU) are anticancer drugs employed in a combination approach. FMM inhibits tyrosine phosphorylation of ErbB4 while 5-FU inhibits cell proliferation. This research aimed to investigate the potential of two compounds, namely (1E,4E)-1,5-bis (4-hydroxyphenyl) penta-1,4-dien-3-one (AC01) and (1E,4E)-1,5-bis (3,4-dihydroxy phenyl) penta-1,4-dien-3-one (AC02), both as individual inhibitors and combination partners with FMM, targeting ErbB4 inhibition. AC01 and AC02 were combined with FMM, which targets ErbB4. The combination of 5-FU with FMM served as a reference in this study. Experimental approach: The research utilized computational simulation methods such as single and multiple ligands simultaneously docking and dynamics. Data analysis was performed using AutoDockTools and gmx_MMPBSA. Findings/Results: Single docking results indicated that 5-FU exhibited the lowest binding affinity, while FMM demonstrated the highest. Simultaneous docking of AC01 and AC02 paired with FMM revealed their binding positions overlapping with the FMM-5-FU workspace. The FMM-AC01 and FMM-AC02 complexes exhibited slightly weaker binding affinities compared to FMM-5-FU. In combination with FMM, AC01 and AC02 occupied the ErbB4 activation loop, whereas 5-FU was outside the activation loop. Furthermore, in their interaction with ErbB4, AC02 exhibited slightly stronger binding than AC01, as confirmed by the average binding free energy calculations from molecular dynamics simulations. Conclusion and implications: In conclusion, computational simulations indicated that both AC01 and AC02 have the potential to act as anticancer candidates, demonstrating ErbB4 inhibitory potential both as individual agents and in synergy with FMM.

La Ode Aman

Netty Ino Ischak

Teti Sutriyati Tuloli

Arfan Arfan

Aiyi Asnawi

Multiple ligands simultaneous molecular docking and dynamics approach to study the synergetic inhibitory of curcumin analogs on ErbB4 tyrosine phosphorylation

多种配体同时分子对接与动力学方法研究姜黄素类似物对ErbB4酪氨酸磷酸化的协同抑制作用

Background and purpose: Alzheimer’s disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer’s Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a large body of recent research has been allocated to the design and development of multi-target-directed ligands that can become effective drug candidates. Experimental approach: A novel series of benzamide derivatives (5a-5l) containing piperidine core were synthesized in the current work. After identification of the chemical structures of the members of this series using 1H NMR, IR, and MS spectra, their anti-acetylcholinesterase activity was assessed by the Ellman᾽s test. Docking studies were also performed to investigate the binding mode and determine the interacting amino acids with the corresponding ligands. Finally, the pharmacokinetic (ADME parameters) of the most potent derivative (5d) was predicted and compared with donepezil. Findings/Results: Compound 5d possessing the fluorine atom substitution at position ortho was the most active compound in these series (IC50 = 13 ± 2.1 nM). This compound demonstrated superior activity than the reference drug donepezil (IC50 = 0.6 ± 0.05 µM). Molecular docking showed a significant hydrogen bonding of the carbonyl group of compounds 5d with tyrosine 121 into the active site of acetylcholinesterase. Fortunately, this compound showed better promising ADME properties than donepezil. Conclusion and implication: The benzamide derivatives introduced in this paper could be proposed as potential anti-acetylcholinesterase.

Ahmad Mohammadi-Farani

Farzaneh Moradi

Amin Hosseini

Alireza Aliabadi

Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents

合成、对接、药代动力学预测及N-(2-(哌啶-1-基)乙基)苯甲酰胺衍生物的乙酰胆碱酯酶抑制活性评价：潜在的抗阿尔茨海默病药物

Background and purpose: Chlorogenic acid (CA) is a natural chemical that promises antiaging activity against photoaging skin damage. This research examined CA activities in mitigating skin photoaging. Experimental approach: UV-exposed human skin fibroblast cells were subjected to CA at 6.25, 12.5, and 25 μg/mL. The protein levels of cell secretion, such as cyclooxygenase (COX)-2, nitric oxide (NO), and interleukin (IL)-6 were measured using ELISA and colorimetry methods. Meanwhile, the mRNA expressions of glutathione peroxidase (GPX)-1, tissue inhibitor metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-1, caspase (CASP)-3, CASP-8, and fibroblast growth factor (FGF)-2 were quantified using the qRT-PCR method. Findings/Results: CA treatment reduced inflammatory and aging biomarkers. CA at 6.25 μg/mL lowered NO, COX-2, and IL-6 levels to 89.44 μmol/L, 8.10 ng/mL, and 62.75 pg/mL, respectively. CA at 25 μg/mL resulted in the most significant down-regulation of MMP-1, CASP-3, and CASP-8 genes’ expression (3.27, 1.25, and 3.59, respectively). Furthermore, treatment with CA at 25 µg/mL demonstrated the most notable activity in up-regulating antioxidant markers, specifically GPX-1, and extracellular matrix (ECM) integrity markers, including TIMP-1 and FGF-2 genes’ expression. Conclusion: CA imposes its anti-aging activity by decreasing inflammatory and aging biomarkers, and increasing cellular antioxidant and ECM integrity.

Ermi Girsang

Chrismis N. Ginting

I Nyoman Ehrich Lister

Wahyu Widowati

Afif Yati

Hanna Sari Widya Kusuma

Rizal Azis

Antiaging properties of chlorogenic acid through protein and gene biomarkers in human skin fibroblast cells as photoaging model

通过蛋白质和基因生物标志物研究绿原酸在人皮肤成纤维细胞光老化模型中的抗衰老特性

Background and purpose: Xanthohumol (Xn), a small molecule found in Humulus lupulus , has shown promise as an anti-cancer compound. This in silico study was performed to understand the mechanism of action of Xn as a natural compound on MEK1/2 by simulation. Experimental approach: After ligand and protein preparation, the best binding energy was determined using Autodock 4.2. Additionally, molecular dynamics simulations of the MEK1/2-Xn and BRaf-MEK1/2-Xn complexes were conducted using GROMACS 2022.1 software and compared to the complexes of MEK1/2-trametinib (Tra) and BRaf-MEK1/2-Tra. Findings/Results: The docking results revealed that the best binding energies for MEK1-Xn (-10.70 Kcal/mol), MEK2-Xn (-9.41 Kcal/mol), BRaf-MEK1-Xn (-10.91 Kcal/mol), and BRaf-MEK2-Xn (-8.54 Kcal/mol) were very close to those of the Tra complexes with their targets, MEK1 and MEK2. Furthermore, Xn was found to interact with serine 222 at the active site of these two kinases. The results of the molecular dynamics simulations also indicated that Xn induced changes in the secondary structure of the studied proteins. The root mean square of proteins and the mean radius of gyration showed significant fluctuations. Conclusion and implications: The findings of the study suggested that Xn, as a novel bioactive compound, potentially inhibits the MEK1/2 function in cancer cells.

Zohreh Gholizadeh Siahmazgi

Shiva Irani

Ali Ghiaseddin

Fereshteh Soutodeh

Zahra Gohari

Jaber Afifeh

Amirreza Pashapouryeganeh

Hilda Samimi

Mahmood Naderi

Parviz Fallah

Vahid Haghpanah

Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation

探索黄腐醇对MEK1/2的抑制潜力：分子对接与动力学模拟研究

Abbreviation	Res Pharma Sci
Journal Impact	2.25
Quartiles(Global)	CHEMISTRY, MEDICINAL(Q3)

ISSN	1735-5362, 1735-9414
h-index	42

Publication Information	Publisher: Wolters Kluwer Medknow Publications，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2009，Proportion of original research papers: 100.00%，Self Citation Rate:9.50%， Gold OA Rate: 96.69%
Journal Fees	$500Details
Average review cycle	网友分享经验：34 Weeks

Research in Pharmaceutical Sciences

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Phytochemicals from Pyrrosia longifolia (Burm. f.) C.V. Morton with antibacterial activity

Multiple ligands simultaneous molecular docking and dynamics approach to study the synergetic inhibitory of curcumin analogs on ErbB4 tyrosine phosphorylation

Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents

Antiaging properties of chlorogenic acid through protein and gene biomarkers in human skin fibroblast cells as photoaging model

Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation

Phytochemicals from Pyrrosia longifolia (Burm. f.) C.V. Morton with antibacterial activity

Multiple ligands simultaneous molecular docking and dynamics approach to study the synergetic inhibitory of curcumin analogs on ErbB4 tyrosine phosphorylation

Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of N-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents

Antiaging properties of chlorogenic acid through protein and gene biomarkers in human skin fibroblast cells as photoaging model

Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation