scholarly journals Peptides with Dual Antimicrobial–Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4245
Author(s):  
Yamil Liscano ◽  
Jose Oñate-Garzón ◽  
Jean Paul Delgado
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Rational Design ◽  
A Priori ◽  
Current Status ◽  
Anticancer Properties ◽  
Anticancer Peptides ◽  
In Silico Studies ◽  
Wide Range ◽  
Improved Stability

Peptides are naturally produced by all organisms and exhibit a wide range of physiological, immunomodulatory, and wound healing functions. Furthermore, they can provide with protection against microorganisms and tumor cells. Their multifaceted performance, high selectivity, and reduced toxicity have positioned them as effective therapeutic agents, representing a positive economic impact for pharmaceutical companies. Currently, efforts have been made to invest in the development of new peptides with antimicrobial and anticancer properties, but the poor stability of these molecules in physiological environments has triggered a bottleneck. Therefore, some tools, such as nanotechnology and in silico approaches can be applied as alternatives to try to overcome these obstacles. In silico studies provide a priori knowledge that can lead to the development of new anticancer peptides with enhanced biological activity and improved stability. This review focuses on the current status of research in peptides with dual antimicrobial–anticancer activity, including advances in computational biology using in silico analyses as a powerful tool for the study and rational design of these types of peptides.

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.

Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

2020 ◽  
Vol 75 (9-10) ◽  
pp. 353-362
Author(s):  
Begüm Nurpelin Sağlık ◽  
Ahmet Mücahit Şen ◽  
Asaf Evrim Evren ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Effects ◽  
Docking Studies ◽  
Benzimidazole Derivatives ◽  
Binding Modes ◽  
Reference Drug ◽  
In Silico Studies ◽  
New Compounds ◽  
Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

In silico studies, synthesis and anticancer activity of novel diphenyl ether-based pyridine derivatives

2018 ◽  
Vol 23 (3) ◽  
pp. 541-554
Author(s):  
Ruchi Verma ◽  
Indira Bairy ◽  
Mradul Tiwari ◽  
G. Varadaraj Bhat ◽  
G. Gautham Shenoy
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Diphenyl Ether ◽  
Pyridine Derivatives ◽  
In Silico Studies

scholarly journals Deciphering the evolution of microbial interactions: in silico studies of two-member microbial communities

2022 ◽  
Author(s):  
Gayathri Sambamoorthy ◽  
Karthik Raman
Keyword(s):  
Microbial Communities ◽  
In Silico ◽  
Microbial Interactions ◽  
Interaction Patterns ◽  
Wild Type ◽  
Community Function ◽  
Evolutionary Forces ◽  
In Silico Studies ◽  
Wide Range ◽  
In The Wild

Microbes thrive in communities, embedded in a complex web of interactions. These interactions, particularly metabolic interactions, play a crucial role in maintaining the community structure and function. As the organisms thrive and evolve, a variety of evolutionary processes alter the interactions among the organisms in the community, although the community function remains intact. In this work, we simulate the evolution of two-member microbial communities in silico to study how evolutionary forces can shape the interactions between organisms. We employ genomescale metabolic models of organisms from the human gut, which exhibit a range of interaction patterns, from mutualism to parasitism. We observe that the evolution of microbial interactions varies depending upon the starting interaction and also on the metabolic capabilities of the organisms in the community. We find that evolutionary constraints play a significant role in shaping the dependencies of organisms in the community. Evolution of microbial communities yields fitness benefits in only a small fraction of the communities, and is also dependent on the interaction type of the wild-type communities. The metabolites cross-fed in the wild-type communities appear in only less than 50% of the evolved communities. A wide range of new metabolites are cross-fed as the communities evolve. Further, the dynamics of microbial interactions are not specific to the interaction of the wild-type community but vary depending on the organisms present in the community. Our approach of evolving microbial communities in silico provides an exciting glimpse of the dynamics of microbial interactions and offers several avenues for future investigations.

scholarly journals A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

2021 ◽  
Vol 11 (19) ◽  
pp. 9139
Author(s):  
Maria Stefania Sinicropi ◽  
Cinzia Tavani ◽  
Camillo Rosano ◽  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Breast Cancer Cell Lines ◽  
Cellular Functions ◽  
Anticancer Properties ◽  
Cycle Arrest ◽  
In Silico Studies ◽  
Ic50 Values ◽  
Mcf 7

Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

scholarly journals Synthesis, biological evaluation, and in silico studies of novel chalcone- and pyrazoline-based 1,3,5-triazines as potential anticancer agents

RSC Advances ◽  
2020 ◽  
Vol 10 (56) ◽  
pp. 34114-34129
Author(s):  
Leydi M. Moreno ◽  
Jairo Quiroga ◽  
Rodrigo Abonia ◽  
Antonino Lauria ◽  
Annamaria Martorana ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Biological Evaluation ◽  
In Silico Studies

A novel series of triazin-chalcones (7,8)a–g and triazin-N-(3,5-dichlorophenyl)pyrazolines (9,10)a–g were synthesized and evaluated for their anticancer activity against nine different cancer strains.

scholarly journals Characterization of a novel peptide mined from the Red Sea brine pools and modified to enhance its anticancer activity

2022 ◽  
Author(s):  
Youssef T. Abdou ◽  
Sheri M. Saleeb ◽  
Khaled Abdel-Raouf ◽  
Mohamed Allam ◽  
Mustafa Adel ◽  
...  
Keyword(s):  
Cell Death ◽  
Anticancer Activity ◽  
Red Sea ◽  
Support Vector ◽  
Cellular Viability ◽  
Migration Ability ◽  
Anticancer Properties ◽  
Skov3 Cells ◽  
In Silico Studies ◽  
Peptide Treatment

Peptide-based drugs have emerged as highly selective and potent cancer therapy. Cancer is one of the leading causes of death worldwide. Multiple approaches have been developed towards cancer treatment, including chemotherapy, radiation, and hormonal therapy; however, such procedures' non-specificity, toxicity, and inefficiency present a hurdle. In this study, we developed a support vector machine (SVM) model to detect the potential anticancer properties of novel peptides through scanning the American University in Cairo Red Sea metagenomics library. Further, we performed in silico studies on a novel 37-mer antimicrobial peptide mined from SVM pipeline analysis. This peptide was further modified to enhance its anticancer activity, analyzed for gene oncology, and subsequently synthesized. The anticancer properties of this 37-mer peptide were evaluated via cellular viability and cell morphology of SNU449, HepG2, SKOV3, and HeLa cells, using MTT assay. Furthermore, we assessed the migration capability of SNU449 and SKOV3 via scratch wound healing assay. Moreover, the targeted selectivity of the peptide for cancerous cells was assessed by testing its hemolytic activity on human erythrocytes. The peptide caused a significant reduction in cellular viability and critically affected the morphology of hepatocellular carcinoma (SNU449 and HepG2), ovarian cancer (SKOV3), and to a limited extent, cervical cancer cell lines (HeLa), in addition to decreasing viability of human fibroblast cell line (1Br-hTERT). Peptide treatment significantly affected the proliferation and migration ability of SNU449 and SKOV3 cells. Annexin V assay was used to evaluate induced cell death upon peptide treatment, attributing programmed cell death (Apoptosis) as the main cause of cell death in SNU449 cells. Finally, we established broad-spectrum antimicrobial properties of the peptide on both gram-positive and gram-negative bacterial strains. Thus, these findings infer the novelty of the peptide as a potential anticancer and antimicrobial agent.

ACES: A co-evolution simulator generates co-varying protein and nucleic acid sequences

2020 ◽  
Vol 18 (06) ◽  
pp. 2050039
Author(s):  
Devin Camenares
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
A Priori ◽  
Software Tool ◽  
Real Data ◽  
Biological Data ◽  
Evolutionary Constraints ◽  
Wide Range ◽  
Nucleic Acid Sequences

Sequence-specific and consequential interactions within or between proteins and/or RNAs can be predicted by identifying co-evolution of residues in these molecules. Different algorithms have been used to detect co-evolution, often using biological data to benchmark a methods ability to discriminate against indirect co-evolution. Such a benchmark is problematic, because not all the interactions and evolutionary constraints underlying real data can be known a priori. Instead, sequences generated in silico to simulate co-evolution would be preferable, and can be obtained using aCES, the software tool presented here. Conservation and co-evolution constraints can be specified for any residue across a number of molecules, allowing the user to capture a complex, realistic set of interactions. Resulting alignments were used to benchmark several co-evolution detection tools for their ability to separate signal from background as well as discriminating direct from indirect signals. This approach can aid in refinement of these algorithms. In addition, systematic tuning of these constraints sheds new light on how they drive co-evolution between residues. Better understanding how to detect co-evolution and the residue interactions they predict can lead to a wide range of insights important for synthetic biologists interested in engineering new, orthogonal interactions between two macromolecules.

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