Isolation of chemical constituents from Nonomuraea species: In vitro and in silico evaluation of its antibacterial properties

Pistacia integerrimais one of twenty species among the genusPistacia. Long horn-shaped galls that develop on this plant are harvested and used in Ayurveda and Indian traditional medicine to make “karkatshringi”, a herbal medicine used for the treatment of asthma and different disorders of respiratory tract. However, until now, the molecular mechanisms of action of “karkatshringi” and its chemical characterization are partially known. This study deals with the isolation and characterization of the active constituents from the methanolic extract ofP. integerrimagalls and it was also oriented to evaluatein vitroandin silicotheir potential enzymatic inhibitory activity against phosphodiesterase-1 (PDE1), a well-known enzyme involved in airway smooth muscle activity and airway inflammation. Our results showed that the methanolic extract ofP. integerrimagalls and some of its active constituents [naringenin (1) and 3,5,7,4′-tetrahydroxy-flavanone (2)] are ablein vitroto inhibit PDE1 activity (59.20 ± 4.95%, 75.90 ± 5.90%, and 65.25 ± 5.25%, resp.) and demonstratein silicoan interesting interaction with this enzymatic site. Taken together, our results add new knowledge of chemical constituents responsible for the biological activity ofP. integerrimaand contextually legitimate the use of this plant in folk medicine.

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Antiproliferative, cholinesterase and phosphodiesterase inhibitory activity of the DCM sub-extract of Uvaria alba: In vitro and in silico perspectives

10.26434/chemrxiv.12924980 ◽

2020 ◽

Author(s):

Mark Tristan J. Quimque ◽

Kin Israel R. Notarte ◽

arianne letada ◽

Rey Arturo T. Fernandez ◽

Kirstin Rhys S. Pueblos ◽

...

Keyword(s):

Secondary Metabolites ◽

Michael Addition ◽

In Silico ◽

Protein Complexes ◽

Chemical Constituents ◽

Myelogenous Leukemia ◽

Btb Domain ◽

Dynamics Simulations ◽

Potential Inhibitors

<div>Aims: To evaluate the in vitro antiproliferative, anticholinesterase and anti-phosphodiesterase activities of the sub-extracts of Uvaria alba (family Annonaceae) and explore putative binding mechanisms of its chemical constituents in silico. <br></div><div><br></div><div>Main methods: U. alba sub-extracts, obtained by solvent-solvent partition, were subjected to antiproliferative and cytotoxicity screening against chronic myelogenous leukemia (K-562) and human cervical cancer (HeLa) cells, respectively. Inhibitory assays against acetylcholinesterase (AChE) and phosphodiesterase (PDE4 B2) enzymes were also performed. The dichloromethane sub-extract (UaD) was chemically profiled using LC-HR-ESIMS-QToF to identify secondary metabolites 1–18. Molecular docking and molecular dynamics simulations were performed to determine the affinity of the putatively annotated metabolites against PDE4 B2B, AChE, ubiquitin specific peptidase 14 (USP14), and Kelch-like ECH-associated protein 1 (Keap1). In addition, DFT calculations were also performed to demonstrate Michael addition reaction between electrophilic cytotoxic metabolites and Cys151 of the Keap1-BTB domain. <br></div><div><br></div><div>Key findings: UaD showed antiproliferative and cytostatic activities against K-562 and HeLa, respectively, and inhibitory activities against AChE and PDE4 B2. Meanwhile, its polyphenolic constituents 3-(3,4-dihydroxybenzyl)-3’,4’,6-trihydroxy-2,4-dimethoxychalcone (8) and grandifloracin (15) showed favorable binding to AChE and Keap1-BTB domain, respectively. The most electrophilic and kinetically stable grandifloracin (15), favorably formed a beta-addition adduct with the Cys151 of Keap1 via Michael addition. The top-ranked ligand-protein complexes attained dynamic stability at 50-ns simulations with high free energy of binding. The top-ranked compounds also conferred favorable in silico pharmacokinetic properties. <br></div><div><br></div><div>Significance: The study highlights the role of U. alba secondary metabolites as potential inhibitors against the aforementioned target proteins in an effort to discover new drug leads for cancer and Alzheimer’s.</div>

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In-silico designing, chemical synthesis, characterization and in-vitro assessment of antibacterial properties of some analogues of curcumin

Microbial Pathogenesis ◽

10.1016/j.micpath.2018.06.030 ◽

2018 ◽

Vol 123 ◽

pp. 89-97 ◽

Cited By ~ 1

Author(s):

Manoj K. Shrivash ◽

Sonali Mishra ◽

UpmaNarain ◽

Jyoti Pandey ◽

Krishna Misra

Keyword(s):

Chemical Synthesis ◽

In Silico ◽

Antibacterial Properties ◽

In Vitro Assessment

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In Vitro and In Silico Evaluation of Biological Properties of Some 1, 3, 4-Oxadiazole Derivatives Against Streptococcus mutans and Their Interaction With Gbp-C by Molecular Docking

Avicenna Journal of Dental Research ◽

10.34172/ajdr.2021.27 ◽

2021 ◽

Vol 13 (4) ◽

pp. 142-147

Author(s):

Behin Omidi ◽

Yasin SarveAhrabi

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Hydrogen Bonds ◽

Streptococcus Mutans ◽

In Silico ◽

Antibacterial Properties ◽

Inhibition Zone ◽

Biological Properties ◽

High Concentrations

Background: The need to replace new drug structures for the treatment of resistant strains has become essential. Streptococcus mutans is one of the most important factors in causing tooth decay. Glucan binding protein-C (Gbp-C) is a crucial mobileular floor protein that is worried in biofilm formation, and 1, 3, 4-oxadiazoles are new antibacterial structures. Accordingly, this study focused on assessing in vitro and in silico activity of our previously synthesized compounds of 1, 3, 4-oxadiazole against S. mutans. Methods: To this end, our previously synthesized derivatives were re-synthesized and prepared, and then antibacterial susceptibility tests were used for inhibition zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) test values. The molecular docking method was also applied to confirm the effect of compounds in interaction with the Gbp-C of S. mutans. Results: All compounds showed different effects against the bacterial sample. Among these, the most effective ones were related to naphthalene (4d), fluorophenyl (4e), and dimethoxyphenyl (4h) derivatives against S. mutans, respectively. Other compounds also had antibacterial properties but to a lesser extent. In the molecular part, compounds 4d and 4h had the highest affinity to inhibit the GbpC-protein. compound 4d with amino acids ASP and GLN established 402 and 391 hydrogen bonds, respectively, and compound 4h with amino acids SER, GLU, THR, and TRP established 347, 360, 449, and 451 hydrogen bonds, respectively. Conclusions: In general, 1, 3, 4-oxadiazoles containing naphthalene and dimethoxy phenyl functional groups in high concentrations can be good alternatives to the existing drugs for eliminating caries-causing tooth mutants that have drug resistance. It seems that more inhibitory effects can be observed on clinical specimens by adding different purposeful groups and increasing the destructive power of oxadiazole-based compounds.

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Antiproliferative, Anticholinesterase and Anti-Phosphodiesterase Inhibitory Properties of the DCM Sub-Extract of Uvaria Alba: Evidence from in Silico Target Fishing and in Vitro Testing

10.26434/chemrxiv.12924980.v1 ◽

2020 ◽

Author(s):

Mark Tristan J. Quimque ◽

Kin Israel R. Notarte ◽

arianne letada ◽

Rey Arturo T. Fernandez ◽

Kirstin Rhys S. Pueblos ◽

...

Keyword(s):

Secondary Metabolites ◽

Michael Addition ◽

In Silico ◽

Protein Complexes ◽

Chemical Constituents ◽

Myelogenous Leukemia ◽

Btb Domain ◽

Dynamics Simulations ◽

Potential Inhibitors

Aims: To evaluate the in vitro antiproliferative, anticholinesterase and anti-phosphodiesterase activities of the sub-extracts of Uvaria alba (family Annonaceae) and explore putative binding mechanisms of its chemical constituents in silico. Main methods: U. alba sub-extracts, obtained by solvent-solvent partition, were subjected to antiproliferative and cytotoxicity screening against chronic myelogenous leukemia (K-562) and human cervical cancer (HeLa) cells, respectively. Inhibitory assays against acetylcholinesterase (AChE) and phosphodiesterase (PDE4 B2) enzymes were also performed. The dichloromethane sub-extract (UaD) was chemically profiled using LC-HR-ESIMS-QToF to identify secondary metabolites 1–18. Molecular docking and molecular dynamics simulations were performed to determine the affinity of the putatively annotated metabolites against PDE4 B2B, AChE, ubiquitin specific peptidase 14 (USP14), and Kelch-like ECH-associated protein 1 (Keap1). In addition, DFT calculations were also performed to demonstrate Michael addition reaction between electrophilic cytotoxic metabolites and Cys151 of the Keap1-BTB domain. Key findings: UaD showed antiproliferative and cytostatic activities against K-562 and HeLa, respectively, and inhibitory activities against AChE and PDE4 B2. Meanwhile, its polyphenolic constituents 3-(3,4-dihydroxybenzyl)-3’,4’,6-trihydroxy-2,4-dimethoxychalcone (8) and grandifloracin (15) showed favorable binding to AChE and Keap1-BTB domain, respectively. The most electrophilic and kinetically stable grandifloracin (15), favorably formed a beta-addition adduct with the Cys151 of Keap1 via Michael addition. The top-ranked ligand-protein complexes attained dynamic stability at 50-ns simulations with high free energy of binding. The top-ranked compounds also conferred favorable in silico pharmacokinetic properties. Significance: The study highlights the role of U. alba secondary metabolites as potential inhibitors against the aforementioned target proteins in an effort to discover new drug leads for cancer and Alzheimer’s.

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Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

Antibiotics ◽

10.3390/antibiotics10050542 ◽

2021 ◽

Vol 10 (5) ◽

pp. 542

Author(s):

Hani A. Alhadrami ◽

Ahmed M. Sayed ◽

Hossam M. Hassan ◽

Khayrya A. Youssif ◽

Yasser Gaber ◽

...

Keyword(s):

Natural Products ◽

In Silico ◽

Structural Information ◽

Chemical Constituents ◽

Rapid Identification ◽

Dependent Manner ◽

Modeling Tools ◽

Clinical Experiments

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract’s antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein–protein and protein–compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

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Antiproliferative, cholinesterase and phosphodiesterase inhibitory activity of the DCM sub-extract of Uvaria alba: In vitro and in silico perspectives

10.26434/chemrxiv.12924980.v2 ◽

2020 ◽

Author(s):

Mark Tristan J. Quimque ◽

Kin Israel R. Notarte ◽

arianne letada ◽

Rey Arturo T. Fernandez ◽

Kirstin Rhys S. Pueblos ◽

...

Keyword(s):

Secondary Metabolites ◽

Michael Addition ◽

In Silico ◽

Protein Complexes ◽

Chemical Constituents ◽

Myelogenous Leukemia ◽

Btb Domain ◽

Dynamics Simulations ◽

Potential Inhibitors

<div>Aims: To evaluate the in vitro antiproliferative, anticholinesterase and anti-phosphodiesterase activities of the sub-extracts of Uvaria alba (family Annonaceae) and explore putative binding mechanisms of its chemical constituents in silico. <br></div><div><br></div><div>Main methods: U. alba sub-extracts, obtained by solvent-solvent partition, were subjected to antiproliferative and cytotoxicity screening against chronic myelogenous leukemia (K-562) and human cervical cancer (HeLa) cells, respectively. Inhibitory assays against acetylcholinesterase (AChE) and phosphodiesterase (PDE4 B2) enzymes were also performed. The dichloromethane sub-extract (UaD) was chemically profiled using LC-HR-ESIMS-QToF to identify secondary metabolites 1–18. Molecular docking and molecular dynamics simulations were performed to determine the affinity of the putatively annotated metabolites against PDE4 B2B, AChE, ubiquitin specific peptidase 14 (USP14), and Kelch-like ECH-associated protein 1 (Keap1). In addition, DFT calculations were also performed to demonstrate Michael addition reaction between electrophilic cytotoxic metabolites and Cys151 of the Keap1-BTB domain. <br></div><div><br></div><div>Key findings: UaD showed antiproliferative and cytostatic activities against K-562 and HeLa, respectively, and inhibitory activities against AChE and PDE4 B2. Meanwhile, its polyphenolic constituents 3-(3,4-dihydroxybenzyl)-3’,4’,6-trihydroxy-2,4-dimethoxychalcone (8) and grandifloracin (15) showed favorable binding to AChE and Keap1-BTB domain, respectively. The most electrophilic and kinetically stable grandifloracin (15), favorably formed a beta-addition adduct with the Cys151 of Keap1 via Michael addition. The top-ranked ligand-protein complexes attained dynamic stability at 50-ns simulations with high free energy of binding. The top-ranked compounds also conferred favorable in silico pharmacokinetic properties. <br></div><div><br></div><div>Significance: The study highlights the role of U. alba secondary metabolites as potential inhibitors against the aforementioned target proteins in an effort to discover new drug leads for cancer and Alzheimer’s.</div>

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In silico and In vitro evaluation of the anti-inflammatory and antioxidant potential of Cymbopogon citratus from North-western Himalayas

10.1101/2020.05.31.124982 ◽

2020 ◽

Cited By ~ 1

Author(s):

Deeksha Salaria ◽

Rajan Rolta ◽

Nitin Sharma ◽

Kamal Dev ◽

Anuradha Sourirajan ◽

...

Keyword(s):

In Silico ◽

Chemical Constituents ◽

Radical Scavenging ◽

Inflammatory Activity ◽

Perennial Herb ◽

Binding Potential ◽

Western Himalayas ◽

Cymbopogon Citratus ◽

Anti Inflammatory

AbstractCymbopogon citratus which is an aromatic perennial herb belonging to family Gramineae is known for its application in food and healthcare industry. The present study attempts to evaluate the potential of essential oil from Cymbopogon citratus (CEO) as an anti-inflammatory and antioxidant agent. CEO showed significant DPPH radical scavenging activity (IC50 - 91.0 ± 9.25 µg/ml), as compared to Ascorbic acid (IC50-33.38 ± 2.29 µg/ml). CEO also exhibited significant in-vitro anti-inflammatory activity with IC50 - 397.11± 1.45µg/ml) as compared to diclofenac sodium (IC50 - 682.98 ± 7.47 µg/ml). Chemical constituents of the oil was determined using Gas Chromatography/Mass Spectroscopy, showed that 8-methyl-3,7-Nonadien-2-one (E), α-Pinene, limonene, citral, limonene oxide and Epoxy-α-terpenyl acetate were the major constituents. The in silico molecular docking study showed phytocompounds of CEO (Caryophyllene oxide and β-caryophyllene) have considerable binding potential with 1HD2 and 5IKQ receptors. PASS prediction of these phytocompounds also confirmed strong anti-inflammatory activity of C. citratus. The ADMET analysis also showed that these phytocompounds are safer to replace the synthetic drugs with side effects. This work establishes the anti inflammatory potential of CEO as an alternative to existing therapeutic approach to treatment of inflammation and also natural source of antioxidant compounds.

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Anti-inflammatory activities of Sigesbeckia glabrescens Makino: combined in vitro and in silico investigations

Chinese Medicine ◽

10.1186/s13020-019-0260-y ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 6

Author(s):

Zhangfeng Zhong ◽

Qianru Zhang ◽

Hongxun Tao ◽

Wei Sang ◽

Liao Cui ◽

...

Keyword(s):

Molecular Docking ◽

In Silico ◽

Inflammatory Diseases ◽

Chemical Constituents ◽

Western Blots ◽

Novel Approach ◽

Inflammatory Mechanism ◽

Mapk Signalling ◽

Anti Inflammatory

Abstract Background Sigesbeckia glabrescens Makino (SG) is one of the important plant origins of Sigesbeckiae herba and has been widely used for the treatment of chronic inflammatory diseases in China. However, the underlying anti-inflammatory mechanism of SG is rarely investigated and reported. There are more than 40 kinds of chemical constituents in SG, but the action of the bioactive compounds of SG is still unclear. Therefore, we aimed to systemically investigate the mechanisms behind the anti-inflammatory properties of SG by combining in vitro and in silico investigations. Methods Cytotoxicity was measured using the 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Nitric oxide (NO) release was detected using the Griess assay. The secretion of pro-inflammatory cytokines and the expression of relevant proteins were assessed using ELISA kits and Western blots, respectively. Molecular docking was performed and scored using AutoDock via a comparison with the molecular docking of N-acetyl-d-glucosamine (NAG). Results In lipopolysaccharides (LPS)-stimulated macrophages, SG significantly inhibited NO, MCP-1, and IL-6 secretion; iNOS expression; and NF-κB activation but did not significantly affect MAPK signalling (p38, ERK, and JNK). Moreover, the results from the molecular docking prediction suggested that over 10 compounds in SG could likely target TLR4, p105, and p65. Conclusions These findings suggest that the anti-inflammatory effects of SG are highly related to the inactivation of NF-κB. Moreover, this study provides a novel approach to investigate the effects of herbal medicine using combined in vitro and in silico investigations.

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HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast

Pharmaceuticals ◽

10.3390/ph14101009 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1009

Author(s):

Winnie Rotich ◽

Nicholas J. Sadgrove ◽

Eduard Mas-Claret ◽

Guillermo F. Padilla-González ◽

Anastasia Guantai ◽

...

Keyword(s):

Reverse Transcriptase ◽

Ellagic Acid ◽

In Silico ◽

Chemical Constituents ◽

Herbal Product ◽

Docking Studies ◽

Prunus Africana ◽

Reverse Transcriptase Enzyme ◽

Hiv 1

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: Acacia nilotica (L.) Willd. ex Delile (currently, Vachelia nilotica (L.) P.J.H Hurter & Mabb.), Adenia gummifera (Harv.) Harms, Anthocleista grandiflora Gilg, Asparagus africanus Lam., Bersama abyssinica Fresen., Clematis hirsuta Guill. & Perr., Croton macrostachyus Hochst. ex Delile, Clutia robusta Pax (accepted as Clutia kilimandscharica Engl.), Dovyalis abyssinica (A. Rich.) Warb, Ekebergia capensis Sparm., Periploca linearifolia Quart.-Dill. & A. Rich., Plantago palmata Hook.f., Prunus africana Hook.f. Kalkman and Rhamnus prinoides L’Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH2Cl2, MeOH, 80% EtOH in H2O, cold H2O, hot H2O and acidified H2O (pH 1.5–3.5). The extracts were analysed using HPLC–MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC50 of 7 μg·mL−1. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin O-rutinoside, pellitorine, mangiferin, isomangiferin, 4-O-coumaroulquinic acid, ellagic acid, ellagic acid O-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL−1, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = −8.55 kcal/mol), followed by magnoflorine (ΔG = −8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B.

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