scholarly journals Three-Component Synthesis of 2-Amino-3-Cyano-4H-Chromenes, In Silico Analysis of Their Pharmacological Profile, and In Vitro Anticancer and Antifungal Testing

2021 ◽  
Vol 14 (11) ◽  
pp. 1110
Author(s):  
Alberto Feliciano ◽  
Omar Gómez-García ◽  
Carlos H. Escalante ◽  
Mario A. Rodríguez-Hernández ◽  
Mariana Vargas-Fuentes ◽  
...  
Keyword(s):  
Active Site ◽  
Antifungal Agents ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Candida Spp ◽  
Topoisomerase Ib ◽  
Three Component Reaction ◽  
Dual Inhibition ◽  
Silico Analysis

Chromenes are compounds that may be useful for inhibiting topoisomerase and cytochrome, enzymes involved in the growth of cancer and fungal cells, respectively. The aim of this study was to synthesize a series of some novel 2-amino-3-cyano-4-aryl-6,7-methylendioxy-4H-chromenes 4a–o and 2-amino-3-cyano-5,7-dimethoxy-4-aryl-4H-chromenes 6a–h by a three-component reaction, and test these derivatives for anticancer and antifungal activity. Compounds 4a and 4b were more active than cisplatin (9) and topotecan (7) in SK-LU-1 cells, and more active than 9 in PC-3 cells. An evaluation was also made of the series of compounds 4 and 6 as potential antifungal agents against six Candida strains, finding their MIC50 to be less than or equal to that of fluconazole (8). Molecular docking studies are herein reported, for the interaction of 4 and 6 with topoisomerase IB and the active site of CYP51 of Candida spp. Compounds 4a–o and 6a–h interacted in a similar way as 7 with key amino acids of the active site of topoisomerase IB and showed better binding energy than 8 at the active site of CYP51. Hence, 4a–o and 6a–h are good candidates for further research, having demonstrated their dual inhibition of enzymes that participate in the growth of cancer and fungal cells.

scholarly journals Design, Molecular Docking And In Silico Analysis Of Analogues Of Chloroquine And Hydroxychloroquine Against SARs-COV-2 Target (6w63.pdb)

2020 ◽  
Author(s):  
Naruka Solomon Yakubu ◽  
Olanike Catherine Poyi ◽  
Ezikiel Olabisi Afolabi
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Target Prediction ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Biologically Active ◽  
Dynamic Simulations ◽  
Comparable Activity ◽  
Silico Analysis

Abstract Computer-aided drug design has been an effective strategy and approach to discover, develop, analyze, accelerate and economize design and development of drugs and biologically active molecules. A total of twelve analogues of chloroquine (CQ) and hydroxychloroquine (HCQ) were designed and virtually analyzed using PyRx software, Molinspiration, Swiss ADME, Swiss-Target Prediction software and ProTox-II-Prediction of toxicity platform. Based on the docking studies carried out using Autodock vina, five analogues; H-368 (-6.0 Kcal/mol), H-372 (--6.0 Kcal/mol), H-156 (-5.9 Kcal/mol), H-139 (-5.7 Kcal/mol), C-136 (-5.7 Kcal/mol) exhibited higher binding affinity compared to HCQ(-5.5 Kcal/mol), while all twelve analogues exhibited higher binding affinity compared to CQ (-4.5Kcal/mol). In silico analysis of toxicity profile of this analogues shows a lower potential to toxicity and a comparable activity on some major isoforms of cytochrome P450. But unlike the parent molecules, both H-139 and H-156 are substrates of P-glycoproteins (P-gp) which implies that these analogues possess high clearance and less pharmacokinetic-related drug-drug interactions compared to the parent molecules. Herein we propose these analogues as potential inhibitors or lead compounds against the coronavirus with a view of conducting more molecular dynamic simulations, synthesizing and conducting in vitro studies on them.

In-Vitro and In-Silico Characterization of Xylose Reductase from Emericella nidulans

2019 ◽  
Vol 13 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Vishal Ahuja ◽  
Aashima Sharma ◽  
Ranju Kumari Rathour ◽  
Vaishali Sharma ◽  
Nidhi Rana ◽  
...  
Keyword(s):  
Production Process ◽  
In Silico ◽  
Xylose Reductase ◽  
In Silico Analysis ◽  
Emericella Nidulans ◽  
Higher Temperature ◽  
In Silico Characterization ◽  
Silico Analysis

Background: Lignocellulosic residues generated by various anthropogenic activities can be a potential raw material for many commercial products such as biofuels, organic acids and nutraceuticals including xylitol. Xylitol is a low-calorie nutritive sweetener for diabetic patients. Microbial production of xylitol can be helpful in overcoming the drawbacks of traditional chemical production process and lowring cost of production. Objective: Designing efficient production process needs the characterization of required enzyme/s. Hence current work was focused on in-vitro and in-silico characterization of xylose reductase from Emericella nidulans. Methods: Xylose reductase from one of the hyper-producer isolates, Emericella nidulans Xlt-11 was used for in-vitro characterization. For in-silico characterization, XR sequence (Accession No: Q5BGA7) was used. Results: Xylose reductase from various microorganisms has been studied but the quest for better enzymes, their stability at higher temperature and pH still continues. Xylose reductase from Emericella nidulans Xlt-11 was found NADH dependent and utilizes xylose as its sole substrate for xylitol production. In comparison to whole cells, enzyme exhibited higher enzyme activity at lower cofactor concentration and could tolerate higher substrate concentration. Thermal deactivation profile showed that whole cell catalysts were more stable than enzyme at higher temperature. In-silico analysis of XR sequence from Emericella nidulans (Accession No: Q5BGA7) suggested that the structure was dominated by random coiling. Enzyme sequences have conserved active site with net negative charge and PI value in acidic pH range. Conclusion: Current investigation supported the enzyme’s specific application i.e. bioconversion of xylose to xylitol due to its higher selectivity. In-silico analysis may provide significant structural and physiological information for modifications and improved stability.

scholarly journals Clinicopathologic features of TDO2 overexpression in renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Quoc Thang Pham ◽  
Daiki Taniyama ◽  
Yohei Sekino ◽  
Shintaro Akabane ◽  
Takashi Babasaki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
In Silico Analysis ◽  
Immunohistochemical Analysis ◽  
Rna Seq ◽  
Anoikis Resistance ◽  
Silico Analysis ◽  
Proliferation And Invasion

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC. (199 words)

Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: synthesis, in-vivo, in-vitro and in-silico analysis

2021 ◽  
pp. 105068
Author(s):  
Devendra Kumar ◽  
Ravi Ranjan Kumar ◽  
Shelly Pathania ◽  
Pankaj Kumar Singh ◽  
Sourav Kalra ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Anti Inflammatory ◽  
Silico Analysis

In-vitro activity of voriconazole (UK-109,496), LY303366 and other antifungal agents against oral Candida spp. isolates from HIV-infected patients

1999 ◽  
Vol 44 (5) ◽  
pp. 697-700 ◽  
Author(s):  
M. Chávez ◽  
S. Bernal ◽  
A. Valverde ◽  
M. J. Gutierrez ◽  
G. Quindós ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Candida Spp ◽  
Oral Candida

scholarly journals IN SILICO STUDY OF THE ANTIMICROBIAL PROFILE OF β-CITRONELLOL: POTENTIAL AS AN ANTIFUNGAL

2019 ◽  
Vol 16 (32) ◽  
pp. 894-898
Author(s):  
D. F. SILVA ◽  
H. D. NETO ◽  
M. D. L. FERREIRA ◽  
A. A. O. FILHO ◽  
E. O. LIMA
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
In Silico Analysis ◽  
Fungal Species ◽  
In Silico Study ◽  
Pass Online ◽  
Therapeutic Alternatives ◽  
Bioactivity Profile ◽  
Silico Analysis

β-citronellol (3,7-dimethyl-6-octen-1-ol) has been exhibiting a number of pharmacological effects that creates interest about its antimicrobial potential, since several substances of the monoterpene class have already demonstrated to possess activity in this profile. In addition, the emergence of fungal species resistant to current pharmacotherapy poses a serious challenge to health systems, making it necessary to search for new effective therapeutic alternatives to deal with this problem. In this study, the antimicrobial profile of β-citronellol was analyzed. The Prediction of Activity Spectra for Substances (PASS) online software was used to study the antimicrobial activity of the β-citronellol molecule by the use of in silico analysis. In contrast, an in vitro antifungal study of this monoterpene was carried out. For this purpose, the Minimum Inhibitory Concentration (MIC) was determined by the microdilution technique in 96-well plates in Saboraud Dextrose Broth/RPMI against sensitive strains of Candida albicans, and this assay was performed in duplicate. In the in silico analysis of the antimicrobial profile, it was revealed that the monoterpene β-citronellol had a diverse antimicrobial bioactivity profile. For the antifungal activity, it presented a percentage value with Pa: 58.4% (predominant) and its MIC of 128 μg/mL, which was equivalent for all strains tested. The in silico study of the β-citronellol molecule allowed us to consider that the monoterpenoid is very likely to be bioactive against agents that cause fungal infections.

Synthesis and antimicrobial activity of aryldiazenyl/arylhydrazono pyrazoles

2021 ◽  
Vol 45 (11-12) ◽  
pp. 1093-1099
Author(s):  
Abdulrhman Alsayari ◽  
Yahya I Asiri ◽  
Abdullatif Bin Muhsinah ◽  
Mohd. Zaheen Hassan
Keyword(s):  
Active Site ◽  
Phenyl Ring ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Docking Studies ◽  
Considerable Effect ◽  
Design Synthesis ◽  
Structure Activity ◽  
Antimicrobial Evaluation

We report the design, synthesis, and in vitro antimicrobial evaluation of functionalized pyrazoles containing a hydrazono/diazenyl moiety. Among these newly synthesized derivatives, 4-[2-(4-chlorophenyl)hydrazono]-5-methyl-2-[2-(naphthalen-2-yloxy)acetyl]-2,4-dihydro-3 H-pyrazol-3-one is a promising antimicrobial agent against Staphylococcus aureus (minimum inhibitory concentration 0.19 μg mL−1). Structure–activity relationship studies reveal that the electronic environment on the distal phenyl ring has a considerable effect on the antimicrobial potential of the hybrid analogues. Molecular docking studies into the active site of S. aureus dihydrofolate reductase also prove the usefulness of hybridizing a pyrazole moiety with azo and hydrazo groups in the design of new antimicrobial agents.

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