Editorial: Molecular and multi-omic approaches in understanding cancer biology and anticancer therapies: current perspectives and new challenges

Peer Reviewe

Novel Papaverine Metal Complexes with Potential Anticancer Activities

Cancer is one of the leading causes of death worldwide. Although several potential therapeutic agents have been developed to efficiently treat cancer, some side effects can occur simultaneously. Papaverine, a non-narcotic opium alkaloid, is a potential anticancer drug that showed selective antitumor activity in various tumor cells. Recent studies have demonstrated that metal complexes improve the biological activity of the parent bioactive ligands. Based on those facts, herein we describe the synthesis of novel papaverine–vanadium(III), ruthenium(III) and gold(III) metal complexes aiming at enhancing the biological activity of papaverine drug. The structures of the synthesized complexes were characterized by various spectroscopic methods (IR, UV–Vis, NMR, TGA, XRD, SEM). The anticancer activity of synthesized metal complexes was evaluated in vitro against two types of cancer cell lines: human breast cancer MCF-7 cells and hepatocellular carcinoma HepG-2 cells. The results revealed that papaverine-Au(III) complex, among the synthesized complexes, possess potential antimicrobial and anticancer activities. Interestingly, the anticancer activity of papaverine–Au(III) complex against the examined cancer cell lines was higher than that of the papaverine alone, which indicates that Au-metal complexation improved the anticancer activity of the parent drug. Additionally, the Au complex showed anticancer activity against the breast cancer MCF-7 cells better than that of cisplatin. The biocompatibility experiments showed that Au complex is less toxic than the papaverine drug alone with IC50 ≈ 111 µg/mL. These results indicate that papaverine–Au(III) complex is a promising anticancer complex-drug which would make it a suitable candidate for further in vivo investigations.Peer Reviewe

Menopause Anxiety and Depression; How Food Can Help?

BACKGROUND: Anxiety and depression are reported as two major frequent and chief complaints among peri-menopausal women in several societies. AIM: The objective of the study was to study the effect of using two dietary supplements to beat depression and anxiety associated with menopause. SUBJECTS AND METHODS: Sixty-six volunteers’ menopausal women participated on the study for 8 weeks, 35 subjects consumed daily cookies prepared mainly from soya flour and flaxseed, and 31 females consumed daily a blend composed mainly of raw unroasted peanut and raw sesame. Follow-up was performed with menopause rating scale, anxiety score, depression score, and biochemical parameters. RESULTS: Soya cookies were rich in plant-based protein and total phenols while blend was a good source of unsaturated fatty acid. Blend consumers showed significant percentage reduction in beck anxiety score and beck depression score after intervention, more than cookies consumers group. The anthropometrics parameters were statistical significant changed on both groups, more on the group who consumed the soya cookies. Soya cookies demonstrated an anti-inflammatory effect, while blend had an antioxidant and anti-inflammatory effects as was shown on the serum assay of interleukin-6 and malondialdehyde as an inflammatory marker and an antioxidant marker, respectively. CONCLUSION: From the results, it can be concluded that the supplementation of products enriched with unsaturated fatty acid was more beneficial to slow down the psychological menopause symptoms than natural estrogen rich product consumption

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 μg/mL, compared to celecoxib drug (IC50 value 251.2 μg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1β. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 μg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.the Faculty of Science, Port Said University and Suez Canal University, EgyptPrincess Nourah bint Abdulrahman University, Riyadh, Saudi Arabiathe Faculty of Medicine, Al-Azhar University, EgyptPeer Reviewe

New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study

Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.Taif UniversityPeer Reviewe

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study

Breast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC50 of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC50 = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC50 = 0.093 µM) compared to Sorafenib (IC50 = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.Faculty of Pharmacy, Suez Canal University, and Faculty of Science, Port Said University, EgyptPrincess Nourah bint Abdulrahman University Researchers SupportingTaif University Researcher

Exploring the antibacterial potential of plant extracts and essential oils against Bacillus thermophilus in beet sugar for enhanced sucrose retention: a comparative assessment and implications

Sugar beet is one of the greatest sources for producing sugar worldwide. However, a group of bacteria grows on beets during the storage process, leading to a reduction in sucrose yield. Our study focused on identifying common bacterial species that grow on beets during manufacturing and contribute to sucrose loss. The ultimate goal was to find a potential antibacterial agent from various plant extracts and oils to inhibit the growth of these harmful bacteria and reduce sucrose losses. The screening of bacterial species that grow on beet revealed that a large group of mesophilic bacteria, such as Bacillus subtilis, Leuconostoc mesenteroides, Pseudomonas fluorescens, Escherichia coli, Acinetobacter baumannii, Staphylococcus xylosus, Enterobacter amnigenus, and Aeromonas species, in addition to a dominant thermophilic species called Bacillus thermophilus, were found to be present during the manufacturing of beets. The application of 20 plant extracts and 13 different oils indicated that the extracts of Geranium gruinum, Datura stramonium, and Mentha spicata were the best antibacterials to reduce the growth of B. thermophilus with inhibition zones equal to 40, 39, and 35 mm, respectively. In contrast, the best active oils for inhibiting the growth of B. thermophilus were Mentha spicata and Ocimum bacilicum, with an inhibitory effect of 50 and 45 mm, respectively. RAPD-PCR with different primers indicated that treating sugar juice with the most effective oils against bacteria resulted in new recombinant microorganisms, confirming their roles as strong antibacterial products. The characterization of Mentha spicata and Ocimum bacilicum oils using GC/MS analysis identified cis-iso pulegone and hexadecanoic acid as the two main bioactive compounds with potential antibacterial activity. An analysis of five genes using DD-PCR that have been affected due to antibacterial activity from the highly effective oil from Mentha spicata concluded that all belonged to the family of protein defense. Our findings indicate that the application of these pure antibacterial plant extracts and oils would minimize the reduction of sucrose during sugar production.Peer Reviewe

Unveiling the antitumor potential of novel N-(substituted-phenyl)-8-methoxycoumarin-3-carboxamides as dual inhibitors of VEGFR2 kinase and cytochrome P450 for targeted treatment of hepatocellular carcinoma

Being the sixth most diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide, liver cancer is considered as a serious disease with a high prevalence and poor prognosis. Current anticancer drugs for liver cancer have drawbacks, such as limited efficacy in later stages of the disease, toxicity to healthy cells, and the potential for drug resistance. There is ample evidence that coumarin-based compounds are potent anticancer agents, with numerous analogues currently being investigated in preclinical and clinical studies. The current study aimed to explore the antitumor potency of a new class of 8-methoxycoumarin-3-carboxamides against liver cancer. Toward this aim, we have designed, synthesized, and characterized a new set of N-(substituted-phenyl)-8-methoxycoumarin-3-carboxamide analogues. The assessment of antitumor activity revealed that the synthesized class of compounds possesses substantial cytotoxicity toward Hep-G2 cells when compared to staurosporine, without significant impact on normal cells. Out of the synthesized compounds, compound 7 demonstrated the most potent cytotoxic effect against Hep-G2 cells with an IC50 of 0.75 µM, which was more potent than the drug staurosporine (IC50 = 8.37 µM). The investigation into the mechanism behind the antiproliferative activity of compound 7 revealed that it interferes with DNA replication and induces DNA damage, leading to cell cycle arrest as demonstrated by a significant decrease in the percentage of cells in the G1 and G2/M phases, along with an increase in the percentage of cells in the S phase. Flow cytometric analysis further revealed that compound 7 has the ability to trigger programmed cell death by inducing necrosis and apoptosis in HepG-2 cells. Further explorations into the mechanism of action demonstrated that compound 7 displays a potent dual-inhibitory activity toward cytochrome P450 and vascular endothelial growth factor receptor-2 (VEGFR-2) proteins, as compared to sorafenib drug. Further, detailed computational studies revealed that compound 7 displays a considerable binding affinity toward the binding cavity of VEGFR2 and CYP450 proteins. Taken together, our findings indicate that the newly synthesized class of compounds, particularly compound 7, could serve as a promising scaffold for the development of highly effective anticancer agents against liver cancer

Resolving sphingolipid isomers using cryogenic infrared spectroscopy

1‐Deoxysphingolipids are a recently described class of sphingolipids that have been shown to be associated with several disease states including diabetic and hereditary neuropathy. The identification and characterization of 1‐deoxysphingolipids and their metabolites is therefore highly important. However, exact structure determination requires a combination of sophisticated analytical techniques due to the presence of various isomers, such as ketone/alkenol isomers, carbon–carbon double‐bond (C=C) isomers and hydroxylation regioisomers. Here we demonstrate that cryogenic gas‐phase infrared (IR) spectroscopy of ionized 1‐deoxysphingolipids enables the identification and differentiation of isomers by their unique spectroscopic fingerprints. In particular, C=C bond positions and stereochemical configurations can be distinguished by specific interactions between the charged amine and the double bond. The results demonstrate the power of gas‐phase IR spectroscopy to overcome the challenge of isomer resolution in conventional mass spectrometry and pave the way for deeper analysis of the lipidome