Health Benefits, Therapeutic Applications, and Recent Advances of Cirsilineol in the Medicine: Potential Bioactive Natural Flavonoids of Genus Artemisia.

BACKGROUND: Herbal medicine and its derived products have been used in the medicine and nutraceutical sectors for the treatment of human disorders and associated secondary complications. Plant-derived products play an important role in our daily life due to their medicinal properties and pharmacological activities. The attention of scientists to natural products has increased due to their significant biological activities. Flavonoids represent one of the most important phytocompounds present in the higher plants, common fruits, vegetables, herbs, wine, juices, and dried fruits. Flavonoids exert potent antioxidant activity by blocking and scavenging free radicals. Cirsilineol, also called 4',5-dihydroxy-3',6,7-trimethoxyflavone, is an active phytochemical of Artemisia vestita, Artemisia monosperma, Artemisia asiatica, and Agrostis gigantea. METHODS: Medicinal importance and pharmacological activities of cirsilineol have been investigated in the present work with their analytical aspects in order to know the biological importance of cirsilineol in medicine. Literature data on cirsilineol were collected and analyzed in the present work to study its therapeutic potential against various human disorders and associated secondary complications. Scientific data were collected from Google, Google Scholar, PubMed, Science Direct, and Scopus and analyzed in the present work using the term herbal medicine, flavonoid and cirsilineol. RESULTS: Medicinal plants containing a significant amount of cirsilineol have biological applications in medicine due to their pharmacological activities. This present work signifies the biological importance of cirsilineol in medicine as it has anti-proliferative, gastroprotective, anti-Helicobacter pylori, anti-diabetic and anti-oxidant activities. Further therapeutic effectiveness of cirsilineol against different types of cancers, including breast carcinoma and lung carcinoma, has been discussed in the present work. The biological importance of cirsilineol against allergic rhinitis, inflammation, coronavirus, immune system, renal cellular membrane and protein glycation has also been discussed in the present work. However, the importance of analytical methods for the isolation and identification of cirsilineol in medicine has also been analyzed. CONCLUSION: This work aimed to summarize the health-beneficial aspects of cirsilineol in medicine which will be beneficial to explore the further therapeutic effectiveness of cirsilineol for the treatment of various forms of human disorders.

A Review on Therapeutic Potential of Indian Herbal Plants to Counter Viral Infection and Disease Pathogenesis

Herbal plant extracts or purified phytocomponents have been extensively used to treat several diseases since ancient times. The Indian Ayurvedic system and Chinese traditional medicines have documented the medicinal properties of important herbs. In Ayurveda, the polyherbal formulation is known to exhibit better therapeutic efficacy compared to a single herb. This review focuses on six key ayurvedic herbal plants namely, Tinospora cordifolia, Withania somnifera, Glycyrrhiza glabra/Licorice, Zingiber officinale, Emblica officinalis and Ocimum sanctum. These plants possess specific phytocomponents that aid them in fighting infections and keeping body healthy and stress-free. Plants were selected due to their reported antimicrobial and anti-inflammatory effects in several diseases and effectiveness in controlling viral pathogenesis. An ad-vanced literature search was carried out using Pubmed and google scholar. Result(s): These medicinal plants are known to exhibit several protective features against various diseases or infections. Here we have particularly emphasized on antioxidant, anti-inflammatory, anti-microbial and immunomodulatory properties which are common in these six plants. Recent literature analysis has revealed Ashwagandha to be protective for Covid-19 too. The formulation from such herbs can exhibit synergism and hence better effectiveness against infection and related dis-eases. The importance of these medicinal herbs becomes highly prominent as it maintains the har-monious balance by way of boosting the immunity in a human body. Further, greater mechanistic analyses are required to prove their efficacy in fighting infectious diseases like Covid-19. It opens the arena for in-depth research of identifying and isolating the active components from these herbs and evaluating their potency to inhibit viral infections as polyherbal formulations.Copyright © 2023 Bentham Science Publishers.

The evolving landscape of pulmonary arterial hypertension clinical trials

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.Copyright © 2022 Elsevier Ltd

The Role of Aquatic Plants in Natural Products and Drug Discovery

Background: Phytochemicals and their derivatives/analogues represent over 50% of the current medicines worldwide in clinical use. Despite a significant contribution to the total bioactive natural plant products, aquatic plants are underestimated, and several species are extinct and in the endangered list. Objective(s): The aim of this review article is to draw the attention of common people and scientists toward a few important contributions of the aquatic plants to natural product chemistry and drug discovery by highlighting the chemical and pharmaceutical aspects of the same. Method(s): The presented data were collected and selected from the literature obtained by an online search for the ethnomedicinal properties, biological activities and bioactive chemical constituents of aquatic plants using Google Scholar, PubMed and Scifinder chemical abstract service. Result(s): The selected literature data revealed that the extract and compounds isolated from several aquatic plants possess significant biological/pharmaceutical properties. For example, the alpha-asarone (24) and asiatic acid (33) isolated from Acorus calamus and Centella asiatica, respectively, exhibited significant neuroprotective effects in vitro and in vivo. The cripowellin A (59), cripowellin C (60), cripowellin B (61) and cripowellin D (62), isolated from Crinum erubescens, exhibited potent antiplasmodial and antiproliferative activities with half maximal inhibitory concentration (IC50) in nanomolar range (11-260 nM). Several other alkaloids from different Crinum species have also shown anticancer properties against different cancer cell lines with IC50 value <5 microM. Alkaloids and resin glycosides, isolated from different Ipomoea species, have displayed significant psychotropic, psychotomimetic, anticancer, and antibacterial activities with IC50 value <5 microM. Conclusion(s): The aquatic plants play a significant role in the discovery of bioactive natural products. Although several biological activities and bioactive compounds have been reported from these plants, further assessment and scientific validation of most of their traditional usages still need to be done. There are several other similar species that are underestimated and not much explored. Many aquatic plants, such as Ipomoea carnea Jacq., Juncus lomatophyllus Spreng., Commelina benghalensis Linn, Gunnera perpensa L., Scirpus maritimus L. and Mentha longifolia (L.) L., may be considered for further evaluation. In addition to these, one should not undermine the potential of Crinum macowanii for COVID-19 pathogenesis, as its chemical constituent lycorine has shown significant SARS-CoV-2 inhibitory potential (EC50, 0.3 muM;SI >129). Furthermore, most rural communities are still using the wetland resources for their cultural, medicinal, economic, domestic, and agricultural needs. Hence, the conservation of aquatic plants and wetlands is an issue of great concern.Copyright © 2023 Bentham Science Publishers.

Synthesis of conjugates of (aR,7S)-colchicine with monoterpenoids and investigation of their biological activity.

Conjugates of the natural alkaloid (aR,7S)-colchicine with bicyclic monoterpenoids and their derivatives were synthesized for the first time. Molecular docking of the synthesized agents in the active site of the main viral protease of the SARS-CoV-2 virus was carried out. The cytotoxic properties of the agents against different cell lines and the ability to inhibit the main viral protease 3CLPro were studied.

Biological Activities of Ruthenium NHC Complexes: An Update.

Ruthenium N-heterocyclic carbene (NHC) complexes have unique physico-chemical properties as catalysts and a huge potential in medicinal chemistry and pharmacology, exhibiting a variety of notable biological activities. In this review, the most recent studies on ruthenium NHC complexes are summarized, focusing specifically on antimicrobial and antiproliferative activities. Ruthenium NHC complexes are generally active against Gram-positive bacteria, such as Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, Listeria monocytogenes and are seldom active against Gram-negative bacteria, including Salmonella typhimurium, Pseudomonas aeruginosa and Escherichia coli and fungal strains of Candida albicans. The antiproliferative activity was tested against cancer cell lines of human colon, breast, cervix, epidermis, liver and rat glioblastoma cell lines. Ruthenium NHC complexes generally demonstrated cytotoxicity higher than standard anticancer drugs. Further studies are needed to explore the mechanism of action of these interesting compounds.

Synthesis and Biological Evaluation of Imadazo[1,2-a]pyrazines as Anticancer and Antiviral Agents through Inhibition of CDK9 and Human Coronavirus.

In this work, novel imadazo[1,2-a]pyrazine derivatives were synthesized and evaluated as CDK9 inhibitors. The results of CDK9 assay showed that the derivatives with pyridin-4-yl in position 2 and benzyl in position 3 of imadazo[1,2-a]pyrazine 3c displayed the most potent CDK9 inhibitory activity with IC50 of 0.16 µM. The anti-proliferative effect of the new compounds was examined against breast cancer (MCF7), colorectal cancer (HCT116), and chronic myelogenous leukaemia (K652) cell lines. The data of MTT assay showed that the cytotoxic effect of the inhibitors is correlated to their inhibitory activity against CDK9. Compound 3c exhibited the most potent cytotoxicity effect with average IC50s of three cell lines of 6.66 µM. The drug likeness properties of 3c were predicated in silico and demonstrated that 3c have reasonable physiochemical and pharmacokinetic properties. Selected derivatives were assessed in antiviral assay against human coronavirus 229E. The results of this assay showed that the derivative with pyridin-4-yl in position 2 and cyclohexyl in position 3 of imadazo[1,2-a]pyrazine 3b exhibited the most potent anti-coronaviral activity with IC50 of 56.96 µM and selectivity index of 7.14. The target predication result revealed that 3b showed high affinity to protease enzyme. Docking studies of 3b with COVID-19 main protease was conducted and showed good binding affinity, which confirmed the in vitro assay data.

Potential Multifunctional Bioactive Compounds from Dysosma versipellis Explored by Bioaffinity Ultrafiltration-HPLC/MS with Topo I, Topo II, COX-2 and ACE2.

Background: Dysosma versipellis (D. versipellis) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown. Purpose: This study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action. Methods: Bioaffinity ultrafiltration coupled to liquid chromatography-mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis, and then further validation was conducted using in vitro inhibition assays and molecular docking. Results: A total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC50 value at 0.36 ± 0.02 µM lower than indomethacin at 0.73 ± 0.07 µM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC50 value at 104.79 ± 8.26 µM comparable to quercetin 3-O-glucoside at 135.25 ± 6.54 µM. Conclusion: We firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants.

Immune response to third SARS-CoV-2 vaccination in seronegative kidney transplant recipients: Possible improvement by mycophenolate mofetil reduction.

Modification of vaccination strategies is necessary to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). This multicenter observational study analyzed the effects of the third SARS-CoV-2 vaccination in previously seronegative KTRs with the focus on temporary mycophenolate mofetil (MMF) dose reduction within propensity matched KTRs. 56 out of 174 (32%) previously seronegative KTRs became seropositive after the third vaccination with only three KTRs developing neutralizing antibodies against the omicron variant. Multivariate logistic regression revealed that initial antibody levels, graft function, time after transplantation and MMF trough levels had an influence on seroconversion (P < .05). After controlling for confounders, the effect of MMF dose reduction before the third vaccination was calculated using propensity score matching. KTRs with a dose reduction of ≥33% showed a significant decrease in MMF trough levels to 1.8 (1.2-2.5) µg/ml and were more likely to seroconvert than matched controls (P = .02). Therefore, a MMF dose reduction of 33% or more before vaccination is a promising approach to improve success of SARS-CoV-2 vaccination in KTRs.

Enzyme-assisted extraction of anthocyanins and other phenolic compounds from blackcurrant (Ribes nigrum L.) press cake: From processing to bioactivities.

The effects of commercial enzymes (pectinases, cellulases, beta-1-3-glucanases, and pectin lyases) on the recovery of anthocyanins and polyphenols from blackcurrant press cake were studied considering two solid:solvent ratios (1:10 and 1:4 w/v). ß-glucanase enabled the recovery of the highest total phenolic content - 1142 mg/100 g, and the extraction of anthocyanins was similar using all enzymes (∼400 mg/100 g). The use of cellulases and pectinases enhanced the extraction of antioxidants (DPPH - 1080 mg/100 g; CUPRAC - 3697 mg/100 g). The freeze-dried extracts presented antioxidant potential (CUPRAC, DPPH), which was associated with their biological effects in different systems: antiviral activity against both non-enveloped viruses (enterovirus coxsackievirus A-9) and enveloped coronaviruses (HCoV-OC43), and cytotoxicity towards cancer cells (A549 and HCT8). No cytotoxic effects on normal human lung fibroblast (IMR90) were observed, and no anti-inflammatory activity was detected in lipopolysaccharides-treated murine immortalised microglial cells.

Investigating the Anti-Viral and Anti-Bacterial activities of Jordanian Medicinal plants: A narrative review

The diversity in Jordan’s flora due to its geographical areas make is well noted in the scientific literature. The challenge of disease and death caused by infectious diseases like viruses and bacteria, and as infectious diseases evolve and pathogens develop resistance to existing pharmaceuticals, the search for new novel leads, possibly with different modes of action, against bacterial and viral diseases has intensified in recent years. The intent of this review is to provide prevalent information on the antibacterial and antiviral potential in medicinal plants in Jordan, mode of action, type of viruses and bacteria, and phytochemical contents. It has been demonstrated by several studies presented in this review that medicinal plants in Jordan are rich in phytochemicals and possess antiviral and antibacterial properties.

Synthesis and Biological Evaluation of Harmirins, Novel Harmine-Coumarin Hybrids as Potential Anticancer Agents.

As cancer remains one of the major health burdens worldwide, novel agents, due to the development of resistance, are needed. In this work, we designed and synthesized harmirins, which are hybrid compounds comprising harmine and coumarin scaffolds, evaluated their antiproliferative activity, and conducted cell localization and cell cycle analysis experiments. Harmirins were prepared from the corresponding alkynes and azides under mild reaction conditions using Cu(I) catalyzed azide-alkyne cycloaddition, leading to the formation of the 1H-1,2,3-triazole ring. Antiproliferative activity of harmirins was evaluated in vitro against four human cancer cell lines (MCF-7, HCT116, SW620, and HepG2) and one human non-cancer cell line (HEK293T). The most pronounced activities were exerted against MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range), while the most selective harmirins were 5b and 12b, substituted at C-3 and O-7 of the ß-carboline core and bearing methyl substituent at position 6 of the coumarin ring (SIs > 7.2). Further experiments demonstrated that harmirin 12b is localized exclusively in the cytoplasm. In addition, it induced a strong G1 arrest and reduced the percentage of cells in the S phase, suggesting that it might exert its antiproliferative activity through inhibition of DNA synthesis, rather than DNA damage. In conclusion, harmirin 12b is a novel harmine and coumarin hybrid with significant antiproliferative activity and warrants further evaluation as a potential anticancer agent.

(-)-6-epi-Artemisinin, a Natural Stereoisomer of (+)-Artemisinin in the Opposite Enantiomeric Series, from the Endemic Madagascar Plant Saldinia proboscidea, an Atypical Source.

Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (-)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (-)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.

Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus.

Natural products of microbial origin have inspired most of the commercial pharmaceuticals, especially those from Actinobacteria. However, the redundancy of molecules in the discovery process represents a serious issue. The untargeted approach, One Strain Many Compounds (OSMAC), is one of the most promising strategies to induce the expression of silent genes, especially when combined with genome mining and advanced metabolomics analysis. In this work, the whole genome of the marine isolate Rhodococcus sp. I2R was sequenced and analyzed by antiSMASH for the identification of biosynthetic gene clusters. The strain was cultivated in 22 different growth media and the generated extracts were subjected to metabolomic analysis and functional screening. Notably, only a single growth condition induced the production of unique compounds, which were partially purified and structurally characterized by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). This strategy led to identifying a bioactive fraction containing >30 new glycolipids holding unusual functional groups. The active fraction showed a potent antiviral effect against enveloped viruses, such as herpes simplex virus and human coronaviruses, and high antiproliferative activity in PC3 prostate cancer cell line. The identified compounds belong to the biosurfactants class, amphiphilic molecules, which play a crucial role in the biotech and biomedical industry.

Mechanistic Actions between Garcinia atroviridis Essential Oil and 2 Deoxy-d-glucose in Cultured PANC-1 Human Pancreatic Cancer Cells.

Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.

Silver Nanoparticles from Annona muricata Peel and Leaf Extracts as a Potential Potent, Biocompatible and Low Cost Antitumor Tool.

Cancer is one of the most prevalent diseases in the world and requires new therapies for its treatment. In this context, the biosynthesis of silver nanoparticles (AgNPs) has been developed to treat different types of tumors. The Annona muricata plant is known for having anticancer activity. Its main compounds present in the leaves, stems and skin, allowing for its use as reducing agents. In this manuscript, AgNPs with leaf extract (AgNPs-LE) and fruit peel extract (AgNPs-PE) of A. muricata were biosynthesized obtaining an average nanoparticle diameter sizes smaller than 50 nm, being 19.63 ± 3.7 nm and 16.56 ± 4.1 nm, and with a surface plasmonic resonance (SPR) at 447 and 448 nm, respectively. The lactone functional group present in the LE and PE extracts was identified by the FTIR technique. The behavior and antiproliferation activity of AgNPs-LE and AgNPs-PE were evaluated in breast, colon and melanoma cancer cell lines. Our results showed that Annona muricata fruit peel, which is a waste product, has an antitumor effect more potent than leaf extract. This difference is maintained with AgNPs where the destruction of cancer cells was, for the first time, achieved using concentrations that do not exceed 3 µg/mL with a better therapeutic index in the different tumor strains. In conclusion, we present a low-cost one-step experimental setup to generate AgNPs-PE whose in-vitro biocompatibility and powerful therapeutic effect make it a very attractive tool worth exploiting.

Better outcome of COVID-19 positive kidney transplant recipients during the unremitting stage with optimized anticoagulation and immunosuppression.

INTRODUCTION: COVID-19 is an ongoing pandemic with high morbidity and mortality and with a reported high risk of severe disease in kidney transplant recipients (KTR). AIM: We aimed to report the largest number of COVID-19-positive cases in KTR in a single center and to discuss their demographics, management, and evolution. METHODS: We enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID-19-positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes. RESULTS: Out of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty-two of them needed hospitalization, of which thirty-one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow-up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%. CONCLUSION: Better outcome of COVID-19-positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.

Identification, protein antiglycation, antioxidant, antiproliferative, and molecular docking of novel bioactive peptides produced from hydrolysis of Lens culinaris.

Bioactive peptides produced from natural sources are considered as strategic target for drug discovery. Hyperglycemia caused protein glycation alters the structure of many tissues that impairs their functions and lead complications diseases in human body. This study investigated the bioactive peptides produced from red and brown Lens culinaris that might inhibit protein glycation to prevent diabetic complications. In this study, red and brown Lens culinaris protein hydrolysates were prepared by tryptic digestion, using an enzyme/substrate ratio of 1:20 (g/g), at 37°C, 12 hr then peptide fractions <3 kDa were filtered by using ultrafiltration membranes. Protective ability against protein glycation, DPPH radical scavenging, and anti-proliferative activities (on HepG2, MCF-7, and PC3 cell lines) of peptide fractions were assayed in vitro. Results showed that glycation was inhibited by peptides from 28.1% to 68.3% in different test model. PC3 cell line was more sensitive to the peptides which showed strong anticancer activity with lower IC50 (0.96 mg/ml). Peptide fractions were sequenced by HPLC-MS-MS. Twenty eight novel peptides sequences was identified. In silico study, two peptides could be developed as a potential bioactive peptides exhibited antiglycation, antioxidant, and antiproliferative activities. PRACTICAL APPLICATIONS: Peptides are becoming an emerging source of medications with the development of new technologies. We have selected Lens Culinaris as one of the rich sources of proteins to explore novel bioactive peptides encapsulated in its seeds. Peptides fractions demonstrated protective ability against protein glycation, strong antioxidant potential, and promising antiproliferative activity. We have identified 28 novel peptides and molecular docking study revealed that some peptides showed strong binding potential to insulin receptor and ACE. Thus, these peptides might be used to manage diabetes complication as well as COVID-19 disease due to their interaction with ACE. However, those peptides needs to be further studied as a potential new drug.

Evaluation of Antiviral, Antibacterial and Antiproliferative Activities of the Endophytic Fungus Curvularia papendorfii, and Isolation of a New Polyhydroxyacid.

An endophytic fungus isolated from Vernonia amygdalina, a medicinal plant from Sudan, was taxonomically characterized as Curvularia papendorfii. Ethyl acetate crude extract of C. papendorfii revealed an important antiviral effect against two viral pathogens, the human coronavirus HCoV 229E and a norovirus surrogate, the feline coronavirus FCV F9. For the last one, 40% of the reduction of the virus-induced cytopathogenic effect at lower multiplicity of infection (MOI) 0.0001 was observed. Selective antibacterial activity was obtained against Staphylococcus sp. (312 µg/mL), and interesting antiproliferative activity with half maximal inhibitory concentration (IC50) value of 21.5 ± 5.9 µg/mL was observed against human breast carcinoma MCF7 cell line. Therefore, C. papendorfii crude extract was further investigated and fractionated. Twenty-two metabolites were identified by gas chromatography coupled to mass spectrometry (GC-MS), and two pure compounds, mannitol and a new polyhydroxyacid, called kheiric acid, were characterized. A combination of spectroscopic methods was used to elucidate the structure of the new aliphatic carboxylic acid: kheiric acid (3,7,11,15-tetrahydroxy-18-hydroxymethyl-14,16,20,22,24-pentamethyl-hexacosa-4E,8E,12E,16,18-pentaenoic acid). Kheiric acid showed an interesting result with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL against meticillin-resistant Staphylococcus aureus (MRSA). Hence, endophytes associated with medicinal plants from Sudan merit more attention, as they could be a treasure of new bioactive compounds.