Bibliometric Analysis of Research on Boesenbergia rotunda, Pinostrobin, and Their Derivatives: Dominance of Southeast Asian Researchers

Pinostrobin, marker compounds from Boesenbergia rotunda with various pharmacological activities, have been studied extensively, including synthesizing its derivatives, which have potent pharmacological activities. This study aims to describe research related to B. rotunda, pinostrobin, and their derivatives. Metadata information was collected from Scopus in August 2022, with three keywords searched for article titles, abstracts, and keywords. Analysis and research mapping were carried out with VOSviewer. The most widely used synonym for the plant name was "Boesenbergia rotunda", in which Norzulaani Khalid from the University of Malaya, Malaysia, mostly reported research with the keywords "Boesenbergia rotunda", "pinostrobin", and "derivative". The majority of researchers come from institutions in Southeast Asia, such as Malaysia, Thailand, and Indonesia. Interestingly, no Chinese researchers have reported studies on this topic. The journals and publishers that publish the most articles with these three keywords are Bioorganic and Medicinal Chemistry Letters and Elsevier, respectively. This information will make it easier for researchers on this topic to find partners for collaboration and determine journals to publish their research results.

La pinostrobina, compuesto de marcadores de Boesenbergia rotunda con diversas actividades farmacológicas, se ha estudiado ampliamente, incluida la síntesis de sus derivados que tienen potentes actividades farmacológicas. Este estudio tuvo como objetivo describir investigaciones relacionadas con B. rotunda, pinostrobina y sus derivados. La información de metadatos se recopiló de Scopus en agosto de 2022, con tres palabras clave buscadas para títulos de artículos, resúmenes y palabras clave. El análisis y el mapeo de la investigación se realizaron con VOSviewer. El sinónimo más utilizado para el nombre de la planta fue "Boesenbergia rotunda", en el que Norzulaani Khalid de la Universidad de Malaya, Malasia, informó principalmente sobre investigaciones con las palabras clave "Boesenbergia rotunda", "pinostrobina" y "derivado". La mayoría de los investigadores provienen de instituciones del sudeste asiático como Malasia, Tailandia e Indonesia. Curiosamente, ningún investigador chino ha informado de estudios sobre este tema. Las revistas y editoriales que más artículos publican con estas tres palabras clave son Bioorganic and Medicinal Chemistry Letters y Elsevier. Esta información facilitará a los investigadores sobre este tema encontrar colaboraciones y determinar las revistas para publicar los resultados de sus investigaciones.

In Silico Analysis of Glycosaminoglycan-Acemannan as a Scaffold Material on Alveolar Bone Healing.

OBJECTIVE: This study aimed to analyze interaction between glycosaminoglycan-acemannan as a scaffold material and toll-like receptor-2 (TLR-2) receptor, which predicted the osteogenesis potency on alveolar bone healing (in silico analysis). MATERIALS AND METHODS: Docking interaction between glycosaminoglycan-acemannan and TLR-2 receptor using the Molegro Virtual Docker (MVD) program. The compounds of glycosaminoglycan-acemannan and TLR-2 receptor with the structure in the form of two- and three-dimensional images were analyzed, as well as the most stable structure. It was observed the interaction of the ligand on the cavity of the TLR-2 receptor structure. The energy required for the ligand and receptor interaction (Moldock score) was calculated with MPD program. RESULTS: The chemical structure shows that glycosaminoglycan-acemannan is capable binding to the TLR-2 receptor with hydrogen bonds and strong steric interaction. The docking results were detected for five cavities where the compound binds to the TLR-2 receptor. The Moldock score of the ligand on the CAS-LYS-LEU-ARG-LYS-ILE-MSE[A] ligand was -95,58 Kcal/mol, that of acemannan was -91,96 Kcal/mol, and for glycosaminoglycan -61,14 Kcal/mol. CONCLUSION: The compound of glycosaminoglycan-acemannan as a scaffold material is able to bind with a TLR-2 target receptor, which predicted osteogenesis activity on alveolar bone healing supported by in silico analysis.

Silver nanoparticles (AgNPs) based selective colorimetric sensor for the detection of D-arabinitol in a urine sample.

D-arabinitol is a sugar alcohol that is a typical metabolite of Candida species. The hydroxy group owned by D-arabinitol can function as a reducing agent that can reduce Ag+ to AgNPs. The resulting colloid is further stabilized by the addition of a capping agent. The capping agent used in this study was a combination of chitosan 1%(w/w) and PEG 6000 1% (w/w) (2:1) v/v. The formation of AgNPs causes an increase in the surface plasmon resonance spectra of the colloid solution at a wavelength of 430 nm with a slight blue shift. At the same time, the color of the solution changes from colorless to yellow colloid so that the absorbance can be observed using a spectrophotometer. The change in the absorbance value of the colloid produced is proportional to the concentration of D-arabinitol added, so that the amount of D-arabinitol in the sample can be quantified. Under optimum conditions, the resulting method shows good linearity with an R2-value of 0.9979 in the concentration range of D-arabinitol 100-2000 µM and Vxo value is 4.30%. The detection limit is 115.11 µM and the quantification limit is 383.70 µM. The repeatability (%RSD) is 0.78-1.94 and the % recovery in addition to urine samples is 93.27-103.70. This method is quite selective for other components present in urine. The analysis time is short, the number of samples required is only small, and does not require an organic solvent, so this method has the potential to be used in determining the levels of D-arabinitol in urine samples.

Predicting the molecular mechanism of glucosamine in accelerating bone defect repair by stimulating osteogenic proteins.

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.

Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction.

OBJECTIVES: Histamine N-methyltransferase (HNMT) is an enzyme that plays a crucial role in the inactivation of histamine in central nervous system, kidneys and bronchi. Inhibition of HNMT is known to have a potential role in treating attention-deficit hyperactivity disorder, memory impairment, mental illness and neurodegenerative illnesses. Therefore, to find potential compounds that could be developed as novel HNMT inhibitors, this study conducted an in silico study of the secondary metabolites of Nigella sativa L and Curcuma xanthorrhiza Roxb. METHODS: In this study, we conducted a molecular docking study of 36 secondary metabolites of N. sativa L and 26 secondary metabolites of C. xanthorrhiza Roxb using an in silico approach targeting HNMT protein (PDB ID: 2AOT) using AutoDockVina software. The prediction of ADMET characteristics was done using the pkCSM Online Tool. RESULTS: This study obtained one metabolite from N. sativa L (longifolene) and seven metabolites from C. xanthorrhiza Roxb {(+)-beta-atlantone, humulene epoxide, (-)-beta-curcumene, (E)-caryophyllene, germacrone, (R)-(-)-xanthorrhizol, and (-)-beta-caryophyllene epoxide} which were predicted to have potential to be developed as HNMT inhibitors. CONCLUSIONS: This study found several secondary metabolites of N. sativa L and C. xanthorrhiza Roxb which had activity as HNMT inhibitors. This research can likewise be utilized as a basis for further research, both in vitro, in vivo, and clinical trials related to the development of secondary metabolites from N. sativa L and C. xanthorrhiza Roxb as novel HNMT inhibitor compounds.

Development, characterization, molecular docking, and in vivo skin penetration of coenzyme Q10 nanostructured lipid carriers using tristearin and stearyl alcohol for dermal delivery.

OBJECTIVES: This study aims to develop coenzyme Q10 nanostructured lipid carriers (NLCs) using tristearin and stearyl alcohol as well as isopropyl palmitate (IPP) as solid and liquid lipid respectively for the dermal delivery system. METHODS: The coenzyme Q10 NLCs were optimized using tristearin, and stearyl alcohol in different concentrations and further characterized by dynamic light scattering (DLS) for particle size, polydispersity index (PDI), zeta potential, differential scanning calorimetry (DSC) and X-ray diffractometry for crystallinity behavior, Fourier transform infrared spectroscopy (FT-IR) for drug-lipid interaction, scanning electron microscopy (SEM) for particle shape, viscometer for viscosity, and pH meter for pH value. Furthermore, entrapment efficiency (EE), drug loading (DL), and skin penetration in vivo were also evaluated while molecular docking was conducted to examine the interaction between coenzyme Q10 and the lipids. RESULTS: The coenzyme Q10 NLCs with tristearin-IPP and stearyl alcohol-IPP as lipid matrix had <1,000 nm particle size, <0.3 PDI, less negative than -30 mV zeta potential, about 41% crystallinity index, and about six as the pH value. Moreover, the EE, DL, viscosity, and in vivo skin penetration of the NLCs using tristearin were higher compared to stearyl alcohol, however, the skin penetration depths for both NLCs were not significantly different. Furthermore, the in silico binding energy of coenzyme Q10-tristearin was lower compared to coenzyme Q10-stearyl alcohol. Both of them showed hydrophobic and van der Waals interaction. CONCLUSIONS: The NLCs of coenzyme Q10 were formulated successfully using tristearin-IPP and stearyl alcohol-IPP for dermal delivery.

Inhibition of Ras and STAT3 activity of 4-(tert-butyl)-N-carbamoylbenzamide as antiproliferative agent in HER2-expressing breast cancer cells.

OBJECTIVES: Human epidermal growth factor receptor type 2 (HER2)-expressing breast cancer patients indicate poor prognosis in disease progression. HER2 overexpression can increase activities of Ras-mitogen activated protein kinase (Ras-MAPK) pathway and Janus Kinase (JAK)-STAT3, increasing breast cancer cell proliferation as demonstrated by marker Ki67. Therapeutic options for HER2-expressing breast cancer are limited and have major side effects, so anticancer development as an antiproliferative is needed. From previous research, synthetic chemical 4-(tert-butyl)-N-carbamoylbenzamide (4TBCB) compound has cytotoxic activity in vitro on HER2-expressing breast cancer cells. This study wanted to determine the mechanism 4TBCB compound in inhibiting HER2 signaling through Rat Sarcoma (Ras) and signal transducer and activator of transcription 3 (STAT3) pathway in HER2-expressing breast cancer cells. METHODS: Breast cancer cells were isolated from the biopsy tissue of breast cancer patients. The isolated cells were cultured and given 4TBCB test compound with three concentrations (0.305, 0.61, and 1.22 mM) and lapatinib 0.05 mM as a comparison compound. Cancer cell cultures were stained with monoclonal antibodies phosphorylated HER2 (pHER2), phosphorylated Ras (pRas), phosphorylated STAT3 (pSTAT3), and Ki67. The expression of pHER2, pRas, pSTAT3, and Ki67 proteins was observed using the immunofluorescence method and the results were compared with control cells, namely cancer cells that were not given 4TBCB and lapatinib but stained with monoclonal antibodies. RESULTS: 4TBCB compounds (0.61 and 1.22 mM) and lapatinib can reduce pHER2, pRas, pSTAT3, and Ki67 expressions compared to control cells. CONCLUSIONS: 4TBCB compounds (0.61 and 1.22 mM) can reduce pHER2, pRas, pSTAT3, Ki67 expressions and predicted to inhibit HER2 signaling through the Ras and STAT3 pathways in HER2-expressing breast cancer cells.

Structure-based virtual screening of bioactive compounds from Indonesian medical plants against severe acute respiratory syndrome coronavirus-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus that causes the infectious disease coronavirus disease-2019. Currently, there is no effective drug for the prevention and treatment of this virus. This study aimed to identify secondary metabolites that potentially inhibit the key proteins of SARS-CoV-2. This was an in silico molecular docking study of several secondary metabolites of Indonesian herbal plant compounds and other metabolites with antiviral testing history. Virtual screening using AutoDock Vina of 216 Lipinski rule-compliant plant metabolites was performed on 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), and spike glycoprotein. Ligand preparation was performed using JChem and Schrödinger's software, and virtual protein elucidation was performed using AutoDockTools version 1.5.6. Virtual screening identified several RdRp, spike, and 3CLpro inhibitors. Justicidin D had binding affinities of -8.7, -8.1, and -7.6 kcal mol-1 on RdRp, 3CLpro, and spike, respectively. 10-methoxycamptothecin had binding affinities of -8.5 and -8.2 kcal mol-1 on RdRp and spike, respectively. Inoxanthone had binding affinities of -8.3 and -8.1 kcal mol-1 on RdRp and spike, respectively, while binding affinities of caribine were -9.0 and -7.5 mol-1 on 3CLpro and spike, respectively. Secondary metabolites of compounds from several plants were identified as potential agents for SARS-CoV-2 therapy.

A novel molecular imprinting polymer for the selective adsorption of D-arabinitol from spiked urine.

In this research, molecular imprinting polymers (MIPs) for D-arabinitol were synthesized using a bulk polymerization method through a noncovalent approach. The MIPs were prepared by using D-arabinitol as a template, acrylamide as a functional monomer, ethylene glycol dimethacrylateas cross-linker, benzoyl peroxide as an initiator and dimethyl sulfoxideas a porogen. MIPS was synthesized in several formulas with a different molar ratio of template to functional monomers and cross-linker. Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) were used to characterize the MIPs produced. A batch rebinding assay was used to test the binding efficiency of each formula. Batch rebinding test results revealed that MIPsF3 with a molar ratio of the template: monomer and crosslinker ratio respectively (1: 4: 25) had the highest binding capacity at 1.56 mgg -1 . The results of isotherm adsorption showed that the MIPs produced followed the Freundlich equation with an R-value of 0.97. The MIPs produced was also selective toward its isomeric compounds (i.e. L-arabinitol, adonitol, xylitol, and glucose). The extraction efficiency of the MIPs against D-arabinitol was 88.98%.

The coronavirus disease 2019 main protease inhibitor from Andrographis paniculata (Burm. f) Ness.

The coronavirus disease 2019 (COVID-19) pandemic has attracted worldwide attention. Andrographis paniculata (Burm. f) Ness (AP) is naturally used to treat various diseases, including infectious diseases. Its Andrographolide has been clinically observed for anti-HIV and has also in silico tested for COVID-19 main protease inhibitors. Meanwhile, the AP phytochemicals content also provides insight into the molecular structures diversity for the bioactive discovery. This study aims to find COVID-19 main protease inhibitor from AP by the molecular docking method and determine the toxicity profile of the compounds. The results obtained two compounds consisting of flavonoid glycosides 5,4'-dihydroxy-7-O-ß -D-pyran-glycuronate butyl ester and andrographolide glycoside 3-O-ß-D-glucopyranosyl-andrographolide have lower free binding energy and highest similarity in types of interaction with amino acid residues compared to its co-crystal ligands (6LU7) and Indinavir or Remdesivir. The toxicity prediction of the compounds also reveals their safety. These results confirm the probability of using AP phytochemical compounds as COVID-19 main protease inhibitors, although further research must be carried out.

Molecular docking of novel 5-O-benzoylpinostrobin derivatives as wild type and L858R/T790M/V948R mutant EGFR inhibitor.

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.

Quantitative Structure-Cytotoxic Activity Relationship 1-(Benzoyloxy)urea and Its Derivative.

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).