Special Issue "Design of Novel Target-Oriented Chemotherapeutic Anti-cancer Agents with ADME Pharmacokinetics"

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Pharmacology and Drug Metabolism".

Deadline for manuscript submissions: 31 July 2023 | Viewed by 2165

Special Issue Editors

Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
Interests: biochemistry; molecular; anti-cancer; natural products
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt
Interests: medicinal chemistry; organic chemistry; computational chemistry; drug design; drug repurposing
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Special Issue Information

Dear Colleagues,

Cancer, as uncontrolled cell proliferation, is the second-leading cause of death worldwide. The present chemotherapy protocols have significant limitations in selectivity and target efficacy. Hence, anti-cancer activity still presents a promising area of research for finding effective and selective anti-cancer agents, so designing novel chemotherapeutics with target-oriented pathways will be of added value. In the context of updated and continuous drug discovery, the term "computer-aided drug design" (CADD) refers to a wide variety of theoretical and computational methodologies that have been employed in predicting the three-dimensional molecular structures of receptors, enzymes, and nucleic acids as molecular models of drug–receptor complexes for designing novel inhibitors with altered recognition and receptor-affinity properties. CADD helps in finding rationalized synthetic compounds or semisynthetic natural compounds against apoptosis, angiogenesis, and metastasis downstream signaling pathway. Additionally, rationalized design helps in studying drug metabolism, drug–target interactions, and ADME pharmacokinetics.

Therefore, this Special Issue deals with designing novel chemotherapeutic agents (synthetic- or natural-based compounds) against both cellular and molecular pathways as selective anti-cancer agents.

Dr. Mohamed S. Nafie
Dr. Ahmed A. Al-karmalawy
Guest Editors

Manuscript Submission Information

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Keywords

  • natural-based compounds
  • anti-cancer
  • target-oriented mechanisms
  • novel synthetic compounds
  • ADME

Published Papers (2 papers)

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Research

Article
Integrating Metabolomics and Gene Expression Underlying Potential Biomarkers Compounds Associated with Antioxidant Activity in Southern Grape Seeds
Metabolites 2023, 13(2), 210; https://doi.org/10.3390/metabo13020210 - 31 Jan 2023
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Abstract
Different southern grape (Muscadine) genotypes (Muscadinia rotundifolia Michx.) were evaluated for their contents of metabolites in ripe berries. The metabolome study identified 331 metabolites in ripening skin and seed tissues. The major chemical groups were organic acids, fatty acyls, polyketides, and organic [...] Read more.
Different southern grape (Muscadine) genotypes (Muscadinia rotundifolia Michx.) were evaluated for their contents of metabolites in ripe berries. The metabolome study identified 331 metabolites in ripening skin and seed tissues. The major chemical groups were organic acids, fatty acyls, polyketides, and organic heterocycle compounds. The metabolic pathways of the identified metabolite were mainly arginine biosynthesis, D-glutamine, D-glutamate metabolism, alanine, aspartate metabolism, aminoacyl-tRNA biosynthesis, and citrate cycle. Principal component analysis indicated that catechin, gallic acid, and epicatechin-3-gallate were the main metabolites existing in muscadine seed extracts. However, citramalic and malic acids were the main metabolites contributing to muscadine skin extracts. Partial least-squares discriminant analysis (VIP > 1) described 25 key compounds indicating the metabolome in muscadine tissues (skin and seed). Correlation analysis among the 25 compounds and oxidation inhibition activities identified five biomarker compounds that were associated with antioxidant activity. Catechin, gallic acid, epicatechin-3-gallate, fertaric acid, and procyanidin B1 were highly associated with DPPH, FRAP, CUPRAC, and ABTS. The five biomarker compounds were significantly accumulated in the seed relative to the skin tissues. An evaluation of 15 antioxidant-related genes represented by the 3-dehydroquinate dehydratase (DHD), shikimate kinase (SK), chalcone synthase (CHS), anthocyanidin reductase (ANR), laccase (LAC), phenylalanine ammonia-lyase (PAL), dihydroflavonol 4-reductase (DFR), 3-dehydroquinate synthase (DHQS), chorismate mutase (CM), flavanone-3-hydroxylase (F3H), cinnamoyl-CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD), leucoanthocyanidin reductase (LAR), gallate 1-β-glucosyltransferase (UGT), and anthocyanidin 3-O-glucosyltransferase (UFGT) encode critical enzymes related to polyphenolics pathway throughout four developmental stages (fruit-set FS, véraison V, ripe-skin R, and ripe-seed; S) in the C5 genotype demonstrated the dramatic accumulation of all transcripts in seed tissue or a developmental stage-dependent manner. Our findings suggested that muscadine grape seeds contain essential metabolites that could attract the attention of those interested in the pharmaceutical sector and the plant breeders to develop new varieties with high nutraceutical value. Full article
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Article
Novel Hybrid Indole-Based Caffeic Acid Amide Derivatives as Potent Free Radical Scavenging Agents: Rational Design, Synthesis, Spectroscopic Characterization, In Silico and In Vitro Investigations
Metabolites 2023, 13(2), 141; https://doi.org/10.3390/metabo13020141 - 17 Jan 2023
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Abstract
Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A [...] Read more.
Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A multiple-step scheme of in vitro radical scavenging assays was carried out to evaluate the antioxidant activity of the synthesized compounds. The results of the DPPH assay demonstrated that the indole-based caffeic acid amides are more active free radical scavenging agents than their benzamide analogues. Compared to Trolox, a water-soluble analogue of vitamin E, compounds 3a, 3f, 3h, 3j, and 3m were found to have excellent DPPH radical scavenging activities with IC50 values of 95.81 ± 1.01, 136.8 ± 1.04, 86.77 ± 1.03, 50.98 ± 1.05, and 67.64 ± 1.02 µM. Three compounds out of five (3f, 3j, and 3m) showed a higher capacity to neutralize the radical cation ABTS•+ more than Trolox with IC50 values of 14.48 ± 0.68, 19.49 ± 0.54, and 14.92 ± 0.30 µM, respectively. Compound 3j presented the highest antioxidant activity with a FRAP value of 4774.37 ± 137.20 μM Trolox eq/mM sample. In a similar way to the FRAP assay, the best antioxidant activity against the peroxyl radicals was demonstrated by compound 3j (10,714.21 ± 817.76 μM Trolox eq/mM sample). Taken together, compound 3j was validated as a lead hybrid molecule that could be optimized to maximize its antioxidant potency for the treatment of oxidative stress-related diseases. Full article
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