scholarly journals Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 751 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Mohammed Al-Azri ◽  
Majid Khan ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Dissociation Constants ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Significant Activity ◽  
Active Compounds ◽  
In Silico Docking ◽  
In Silico Studies ◽  
First Time

Fourteen triterpene acids, viz., three tirucallane-type (1–3), eight ursane-type (4–11), two oleanane-type (12, 13) and one lupane type (21), along with boswellic aldehyde (14), α-amyrine (15), epi-amyrine (16), straight chain acid (17), sesquiterpene (19) and two cembrane-type diterpenes (18, 20) were isolated, first time, from the methanol extract of Boswellia elongata resin. Compound (1) was isolated for first time as a natural product, while the remaining compounds (2‒21) were reported for first time from B. elongata. The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (1–5, 11, 19 and 20) were further screened for in vitro α-glucosidase inhibitory activity. Compounds 3–5 and 11 showed significant activity against α-glucosidase with IC50 values ranging from 9.9–56.8 μM. Compound 4 (IC50 = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by 11 (IC50 = 14.9 ± 1.31 μM), 5 (IC50 = 20.9 ± 0.05 μM) and 3 (IC50 = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds 3–5 and 11 were carried out to investigate their mechanism (mode of inhibition and dissociation constants Ki). All compounds were found to be non-competitive inhibitors with Ki values in the range of 7.05 ± 0.17–51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.

Indane-1,3-diones: as potential and selective α-glucosidase inhibitors, their synthesis, in vitro and in silico studies.

2020 ◽  
Vol 16 ◽  
Author(s):  
Asma Mukhtar ◽  
Shazia Shah ◽  
Kanwal ◽  
Shehryar Hameed ◽  
Khalid Mohammed Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Synthetic Molecules ◽  
Ic50 Values

Background: Diabetes mellitus is one the most chronic metabolic disorder. Since past few years our research group had synthesized and evaluated libraries of heterocyclic compounds against α and β-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and βglucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Method: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and β-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against α-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β-glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

In Vitro, In Silico and Ex Vivo Studies of Dihydroartemisinin Derivatives as Antitubercular Agents

2019 ◽  
Vol 19 (8) ◽  
pp. 633-644 ◽  
Author(s):  
Komal Kalani ◽  
Sarfaraz Alam ◽  
Vinita Chaturvedi ◽  
Shyam Singh ◽  
Feroz Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Silico ◽  
Ex Vivo ◽  
Virulent Strain ◽  
Infection Model ◽  
Mouse Bone Marrow ◽  
Significant Activity ◽  
Macrophage Infection ◽  
In Silico Studies

Introduction: As a part of our drug discovery program for anti-tubercular agents, dihydroartemisinin (DHA-1) was screened against Mtb H37Rv, which showed moderate anti-tubercular activity (>25.0 µg/mL). These results prompted us to carry out the chemical transformation of DHA-1 into various derivatives and study their antitubercular potential. Materials and Methods: DHA-1 was semi-synthetically converted into four new acyl derivatives (DHA-1A – DHA-1D) and in-vitro evaluated for their anti-tubercular potential against Mycobacterium tuberculosis H37Rv virulent strain. The derivatives, DHA-1C (12-O-(4-nitro) benzoyl; MIC 12.5 µg/mL) and DHA-1D (12-O-chloro acetyl; MIC 3.12µg/mL) showed significant activity against the pathogen. Results: In silico studies of the most active derivative (DHA-1D) showed interaction with ARG448 inhibiting the mycobacterium enzymes. Additionally, it showed no cytotoxicity towards the Vero C1008 cells and Mouse bone marrow derived macrophages. Conclusion: DHA-1D killed 62% intracellular M. tuberculosis in Mouse bone marrow macrophage infection model. To the best of our knowledge, this is the first-ever report on the antitubercular potential of dihydroartemisinin and its derivatives. Since dihydroartemisinin is widely used as an antimalarial drug; these results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non-toxic natural product.

Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Mahboob Ali ◽  
Momin Khan ◽  
Khair Zaman ◽  
Abdul Wadood ◽  
Maryam Iqbal ◽  
...  
Keyword(s):  
In Silico ◽  
Enzyme Inhibitors ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Type Ii Diabetes Mellitus ◽  
Spectroscopic Techniques ◽  
Chalcone Derivatives ◽  
In Silico Studies ◽  
Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

scholarly journals Ethers and esters derived from apocynin avoid the interaction between p47phox and p22phox subunits of NADPH oxidase: evaluation in vitro and in silico

2013 ◽  
Vol 33 (4) ◽  
Author(s):  
Martha Edith Macías-Pérez ◽  
Federico Martínez-Ramos ◽  
Itzia Irene Padilla-Martínez ◽  
José Correa-Basurto ◽  
Lowell Kispert ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
In Silico ◽  
Transmembrane Protein ◽  
Vascular Diseases ◽  
Docking Study ◽  
Free Radical Scavengers ◽  
Phenyl Ester ◽  
Paramagnetic Resonance ◽  
In Silico Studies

NOX (NADPH oxidase) plays an important role during several pathologies because it produces the superoxide anion (O2•−), which reacts with NO (nitric oxide), diminishing its vasodilator effect. Although different isoforms of NOX are expressed in ECs (endothelial cells) of blood vessels, the NOX2 isoform has been considered the principal therapeutic target for vascular diseases because it can be up-regulated by inhibiting the interaction between its p47phox (cytosolic protein) and p22phox (transmembrane protein) subunits. In this research, two ethers, 4-(4-acetyl-2-methoxy-phenoxy)-acetic acid (1) and 4-(4-acetyl-2-methoxy-phenoxy)-butyric acid (2) and two esters, pentanedioic acid mono-(4-acetyl-2-methoxy-phenyl) ester (3) and heptanedioic acid mono-(4-acetyl-2-methoxy-phenyl) ester (4), which are apocynin derivatives were designed, synthesized and evaluated as NOX inhibitors by quantifying O2•− production using EPR (electron paramagnetic resonance) measurements. In addition, the antioxidant activity of apocynin and its derivatives were determined. A docking study was used to identify the interactions between the NOX2′s p47phox subunit and apocynin or its derivatives. The results showed that all of the compounds exhibit inhibitory activity on NOX, being 4 the best derivative. However, neither apocynin nor its derivatives were free radical scavengers. On the other hand, the in silico studies demonstrated that the apocynin and its derivatives were recognized by the polybasic SH3A and SH3B domains, which are regions of p47phox that interact with p22phox. Therefore this experimental and theoretical study suggests that compound 4 could prevent the formation of the complex between p47phox and p22phox without needing to be activated by MPO (myeloperoxidase), this being an advantage over apocynin.

scholarly journals MCF-7 Human Breast Adenocarcinoma Anticancer and Antimicrobial, in silico Docking and ADME Prediction Studies of Furan Moiety Containing Substituted 2-Aminopyrimidine Derivatives

2021 ◽  
Vol 33 (7) ◽  
pp. 1504-1512
Author(s):  
Manju Mathew ◽  
Muthuvel Ramanathan Ezhilarasi
Keyword(s):  
In Silico ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Bacterial Strains ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Furan Moiety ◽  
Different Strains

A series of 4(5-(4-chlorophenyl)furan-2-yl)-6-phenylpyrimidin-2-amine derivatives (5a-h) were synthesized from 2-(4-chlorophenyl)-5-styrylfuran (3a-h) with guanidine nitrate in absolute ethanol under conventional method and evaluated for their in vitro anticancer, antimicrobial activities and in silico studies. The chemical structure of the furan moiety containing substituted amino pyrimidine derivatives (5a-h) were elucidated from spectroscopic analysis like infrared, 1H & 13C NMR spectral data and CHN analysis. in silico docking studies were predicted for the synthesized compounds (5a-h) using bacterial protein 1UAG and in silico ADME predictions were also carried for the synthesized compounds (5a-h). The in vitro anticancer study was carried the compound 5b by MMT assay. Compound 5b shows the LC50 value of 120.15 ± 0.003 μg/mL. in vitro Antimicrobial activities were screened for the compounds (5a-h) using different strains. Compound 5h has electron withdrawing group in benzene ring substituted in the para position showed good antimicrobial activity against all the bacterial strains and fungal strains. in silico studies, compound 5h shows excellent docking score (-9.7 kcal/mol) compared with ciprofloxacin (-7.8 kcal/mol).

scholarly journals Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4342
Author(s):  
Begüm Nurpelin Sağlık ◽  
Osman Cebeci ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
Serkan Levent ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
In Silico ◽  
Drug Targets ◽  
Binding Property ◽  
Spectroscopic Techniques ◽  
Design Synthesis ◽  
Piperazine Derivatives ◽  
In Silico Studies ◽  
Mao A

Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as 1H-NMR, 13C-NMR and HRMS. Moreover, the prediction of ADME (Absorption, Distribution, Metabolism, Elimination) parameters for all of the compounds were performed using in silico method. According to the enzyme inhibition results, the synthesized compounds showed the selectivity against MAO-A enzyme inhibition. Compounds 3c, 3d and 3e displayed significant MAO-A inhibition potencies. Among them, compound 3e was found to be the most effective derivative with an IC50 value of 0.057 ± 0.002 µM. Moreover, it was seen that this compound has a more potent inhibition profile than the reference inhibitors moclobemide (IC50 = 6.061 ± 0.262 µM) and clorgiline (IC50 = 0.062 ± 0.002 µM). In addition, the enzyme kinetics were performed for compound 3e and it was determined that this compound had a competitive and reversible inhibition type. Molecular modeling studies aided in the understanding of the interaction modes between this compound and MAO-A. It was found that compound 3e had significant and important binding property.

1,3,4-Thiadiazolo (3,2-Α) Pyrimidine-6-Carbonitrile Scaffold as PARP1 Inhibitors.

2020 ◽  
Vol 21 ◽  
Author(s):  
Elizabeth Eldhose ◽  
Kaviarasan Lakshmanan ◽  
Praveen T. Krishnamurthy ◽  
Kalirajan Rajagopal ◽  
Manal Mohammed ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Activities ◽  
Docking Study ◽  
Binding Mode ◽  
Oral Toxicity ◽  
Standard Drug ◽  
In Silico Docking

Background: 1,3,4-thiadiazolo pyrimidine is a lead molécule which is versatile for a wide variety of biological activities and in continuation of our interest in establishing some novel heterocyclic compounds for antitumor activity. Objective: The objective of the study was to synthesize series of 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] - [1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivative and evaluated for their possible in vitro and in vivo anticancer activity. Methods: Herein we report the synthetic scheme which was followed for the preparation of a series of title compounds B1- B9 is outlined in the scheme 1. The intermediate 5-[(naphthalen-2- yloxy)methyl]-1,3,4-thiadiazolo-2-amine was prepared by heating 2-naphthoxyacetic acid and thiosemicarbazide in presence of phosphoryl chloride at a temperature of 65 - 750C. The obtained compound reacted with malononitrile and appropriate amount of aromatic and heteroaromatic aldehydes in refluxing ethanol yielded 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives (B1 – B9). The purity of synthesized compounds ensured by various spectral analysis. Results: In in-silico molecular docking studies compounds B3 and B9 show binding affinity like known PARP1 inhibitor olaparib. The cellular evaluation indicates that the anticancer activity of compounds B1, B3, B9 is significant when compared to standard drug (olaparib) against MDA-MB-232 cell line and compounds B3, B6, B7 are most active against MCF-7 cell lines. The most active compound B3 was subjected to acute oral toxicity studies by OECD 423 guidelines and in-vivo anti-cancer studies were carried out using DMBA induced model. Conclusion: The in-silico docking study of the newly synthesized compounds were performed, the results showed good binding mode in the active site of PARP1 enzyme. In-silico ADME properties of synthesized compounds were also studied and showed good drug like properties.

scholarly journals Facile One-Pot Multicomponent Synthesis of Pyrazolo-Thiazole Substituted Pyridines with Potential Anti-Proliferative Activity: Synthesis, In Vitro and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3103
Author(s):  
Islam H. El El Azab ◽  
Rania B. Bakr ◽  
Nadia A. A. Elkanzi
Keyword(s):  
Cell Lines ◽  
In Silico ◽  
Topoisomerase Ii ◽  
Human Cancer ◽  
Docking Simulation ◽  
Cytotoxic Potential ◽  
One Pot ◽  
In Silico Docking ◽  
In Silico Studies

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4, via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates (5–16). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5–13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC50 = 17.50–61.05 µM, especially the naphthyridine derivative 7, which exhibited the most cytotoxic potential towards the tested cell lines (IC50 = 14.62–17.50 µM) compared with the etoposide (IC50 = 13.34–17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.

scholarly journals A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 184 ◽  
Author(s):  
Anca-Maria Borcea ◽  
Gabriel Marc ◽  
Ioana Ionuț ◽  
Dan C. Vodnar ◽  
Laurian Vlase ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Study ◽  
Biological Evaluation ◽  
Antifungal Drugs ◽  
Biologically Active ◽  
Molecular Docking Study ◽  
Candida Spp ◽  
In Silico Admet ◽  
In Silico Studies

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14α-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.

scholarly journals Synthesis, Characterization, In-Silico Docking Study and In-Vitro AntiInflammatory Activities of Novel Chalcone Derivatives

2021 ◽  
Vol 3 (2) ◽  
pp. 1-6
Author(s):  
R Bharathi ◽  
◽  
N Santhi ◽  
Keyword(s):  
In Silico ◽  
Aromatic Aldehydes ◽  
Docking Study ◽  
Docking Studies ◽  
In Silico Docking ◽  
Therapeutic Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Important Activity

A series of chalcones were synthesised by condensation of appropriate acetophenones with appropriate aromatic aldehydes, and their anti-inflammatory activities were investigated. In comparison to standard drugs, some have been found to have important activity. In silico docking, tests on chalcones were shown to be more selective to COX-2. Further anti-inflammatory results were supported by docking studies with COX-2. The results from the anti-inflammatory and docking indicate that the synthesised compounds 3b, 3g and 3h can be seen as therapeutic drugs.

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