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Yasser O Mosaad,1 Mohammed Abdalla Hussein,2 Hayam Ateyya,3,4 Ahmed H Mohamed,5 Ali A Ali,6 Alaa Ramadan Youssuf,7 Michael Wink,8 Amal A El-Kholy9 1Department of Pharmacy, Practice & Clinical Pharmacy, Faculty of Pharmacy, Future University, Cairo, Egypt; 2Department of Biotechnology, Faculty of Applied Health Science, October 6th University, October 6th City, Egypt; 3Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt; 4Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Future University, Cairo, Egypt; 5Department of Radiology and Medical Imaging, Faculty of Applied Health Science Technology, October 6th University, October 6th City, Egypt; 6Food Sciences Department, Faculty of Agriculture, Ain Shams University, Cairo, Egypt; 7Consultant and Head of Cardiology Department, AL-AHRAR Teaching Hospital, Zagazig University, Zagazig, Egypt; 8Heidelberg University, Institute of Pharmacy and Molecular Biotechnology, Heidelberg, Germany; 9Department of Clinical Pharmacy, Faculty of Pharmacy, Ain-Shams University, Cairo, EgyptCorrespondence: Mohammed Abdalla Hussein, Faculty of Applied Health Sciences Technology, October 6th University, October 6th City, Egypt, Tel +20 1224832580, Email prof.husseinma@o6u.edu.egIntroduction: Cysteamine, a powerful endogenous antioxidant, is produced mostly by the vanin-1 with pantetheinase activity. With regard to glycemic, inflammatory, and redox factors, the current study sought to evaluate the association between the expression of the vanin-1 gene, oxidative stress, and inflammatory and iNOS signaling pathway in obese diabetic patients.Methods: We enrolled 67 male subjects with an average age of 53.5 ± 5.0 years, divided into 4 groups according to the WHO guideline. We determined their plasma levels of glucose, insulin, IRI, HbA1c, TC, TG, HDL-C, TNF- α, MCP-1, TGF-β 1, SOD, CAT, and TBARs, as well as expression of the iNOS and Vanin1 genes.Results: Overweight and obese class I and II diabetics had significantly higher levels of plasma glucose, insulin, HbA1c, TNF-α, MCP-1, TGF-β 1, CAT, and TBAR as well as iNOS and vanin-1 gene expression compared to healthy control individuals. In addition, as compared to healthy control individuals, overweight obese class I and II diabetics’ plasma HDL-C levels and blood SOD activity were significantly lower. In addition, ultrasound and computed tomography showed that the presence of a mild obscuring fatty liver with mild hepatic echogenicity appeared in overweight, class I and II obese diabetic patients.Conclusion: These findings provide important information for understanding the correlation between Vanin 1 and glycemic, inflammatory, and redox factors in obese patients. Furthermore, US and CT analysis were performed to visualize the observed images of fatty liver due to obesity.Graphical Abstract: Keywords: overweight, BMI, obese diabetic patients, iNOS, vanin-1, MCP-1, US, CT

(1) Background: Type 2 diabetes mellitus (T2DM) is one of the rapidly growing healthcare problems, and several vitamin D receptor (VDR) polymorphisms seem to modulate the risk of T2DM. Our research was designed to investigate the allelic discrimination of VDR polymorphisms and T2DM occurrence risk. (2) Methods: This case-control research included 156 patients with T2DM and 145 healthy control subjects. Most of the study population were males 56.6% vs. 62.8% in the case and control groups, respectively. Genotyping for VDR single nucleotide polymorphisms (SNPs), rs228570 (Fok1), rs7975232 (Apa1), and rs1544410 (Bsm1) was compared between both groups. (3) Results: There was a negative link between vitamin D levels and insulin sensitivity. A significant difference was noted in the allelic discrimination of VDR polymorphism rs228570 and rs1544410 between the study groups (p < 0.001). No difference was observed in the allelic discrimination of VDR polymorphism rs7975232 between the groups (p = 0.063). Moreover, T2DM patients had significantly higher levels of fasting blood sugar (FBS), glycated hemoglobin HbA1c, 2-h post-prandial blood sugar (PP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), total cholesterol, and triglycerides (p < 0.001), while High-Density Lipoprotein (HDL) Cholesterol (HDL-C) was significantly decreased (p = 0.006). (4) Conclusions: VDR polymorphisms had a positive association with T2DM risk among the Egyptian population. Further large-scale research using deep sequencing of samples is strongly urged to investigate different vitamin D gene variants and interactions, as well as the influence of vitamin D on T2DM.

Amal A Mohamed,1 Alshymaa Hassnine,2 Amr Elsayed,2 Mahmoud Montaser,3 Yasmeen Ismail,4 Ahmed El-Demery,5 Eman Sultan,6 Rania S Abdel Aziz,7 Eman Eldemiry,8 Radwa Hagag,9 Amal A El-Kholy,10 Eman Salah11 1Biochemistry and Molecular Biology Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt; 2Gastroenterology and Tropical Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt; 3Department of Dermatology, Andrology and STDs, Faculty of Medicine, Minia University, Minia, Egypt; 4Clinical Pharmacology Department, Faculty of Medicine, Benha University, Benha, Egypt; 5Biochemistry Department, Faculty of Medicine, October 6 University, 6th of October City, Egypt; 6Clinical Nutrition Department, National Nutrition Institute, Cairo, Egypt; 7Clinical and Chemical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 8Faculty of Pharmacy, Fellow of Clinical Pharmacology, Cairo University Hospitals, Giza, Egypt; 9Pharmacy Practice and Clinical Pharmacy Department, Faculty of Pharmacy, Egyptian Russian University, Badr City, Egypt; 10Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; 11Department of Dermatology, Andrology, Sexual Medicine and STDs, Faculty of Medicine, Helwan University, Cairo, EgyptCorrespondence: Amal A El-KholyClinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptTel +201060355448Email Amal.elkhouly@pharma.asu.edu.egBackground: Acne vulgaris (AV) is a chronic inflammatory disease that affects the pilosebaceous unit. Leptin (LEP) gene polymorphisms is associated with higher risk of multiple disorders. Insulin-like growth factor-1 (IGF-1) exerts comedogenic effect by stimulating the sebaceous glands. Isotretinoin is an effective oral therapy for AV with many side effects including hyperlipidemia and increased serum levels of liver enzymes.Purpose: To evaluate the impact of LEP gene rs7799039 polymorphism in acne patients’ clinical response lipid profile and liver enzymes following 6 months oral isotretinoin therapy in Egyptian AV patients.Methods: One hundred eligible AV patients received 0.5 mg/kg oral isotretinoin for 6 months. Patients’ demographics and clinical data were obtained. Body mass index (BMI), lipid profile, liver enzymes and IGF-1 were measured at baseline and after 6 months of therapy. Genotyping was done for LEP gene rs 7799039.Results: Six month administration of oral isotretinoin in Egyptian AV patients is associated with significantly elevated aspartate transaminase (AST) in CC and AC genotypes (P< 0.001). Significant alanine aminotransferase (ALT) elevation was observed in CC, AC and AA genotypes (P < 0.001, 0.004, 0.002, respectively). Total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) were elevated significantly P< 0.001) in the three genotypes. IGF-1 was decreased significantly in CC and AC genotypes (P< 0.001). CC genotype is associated with highest response (P< 0.001).Conclusion: LEP rs7799039 gene had an impact on the clinical response, lipid profile and liver enzymes in AV patients treated with oral isotretinoin. LEP rs7799039 CC genotype is predicted to be the treatment candidate for 6 month oral isotretinoin.Keywords: leptin, IGF-1, lipid, isotretinoin, liver enzymes, LEP, insulin-like growth factor-1

Background One of the crucial functions of the immune system is to prevent tumorigenesis, yet cancer occurs when malignant cells manage to evade immune surveillance via multiple strategies. Accordingly, this study aimed at assessing the potential significance of the novel immune checkpoint B and T lymphocyte attenuator (BTLA) as a prognostic marker in acute myeloid leukemia (AML), in addition to how it relates to response to treatment and patients’ survival. Thus, mRNA expression of BTLA was investigated on peripheral blood in 60 AML patients and 15 healthy controls. Results BTLA expression was found to be significantly elevated (p = 0.024) in the tested AML cases in comparison with healthy controls. Moreover, BTLA was over-expressed in the CD13, CD33, and HLA-DR positive cases as compared to their negative counterparts (p = 0.003; p p = 0.001, respectively), and cases showing BTLA over-expression had significantly poorer overall survival times (p = 0.001) as confirmed by Kaplan–Meier survival analysis. Conclusion These observations suggest that BTLA over-expression may be associated with reduced immunity against tumors and could be recommended as a promising biomarker for unfavorable prognosis in AML.

Sorafenib is an FDA approved chemotherapeutic against hepatocellular carcinoma (HCC) yet associated with various resistance mechanisms. The role of high glucose status on sorafenib action is still to be elucidated. This study clarifies such interaction, taking HepG2 cell lines as HCC models, MALAT1 and H19 as molecular players. HepG2 cell lines were purchased and classified into 8 groups. High glucose status was set by using d-glucose (33 mM) with insulin (1 µM). Mannitol (27.5 mM) was used as a negative osmotic control. Sorafenib was prepared at 15 µM and 20 µM. Cellular viability was assessed with MTT viability assay. Then, with trypan blue viability assay, the results were double checked and HepG2 morphology was examined by optical microscopy. MALAT1 and H19 RQs were assessed by real time PCR (RT-PCR). Results show that in comparison with sorafenib impact on HepG2, high glucose status drops cellular viability to 83.13 % (p 0.01). With hyperosmolar mannitol, it decreases cellular viability to 72.89 % (p 0.001). Regarding the molecular impact, hyperosmolar mannitol with sorafenib elevates both MALAT1 and H19 RQs. Yet, high glucose status elevates MALAT1and declines H19 (p 0.05 and p 0.001 for MALAT1 and H19 comparisons respectively). Therefore, the impact of high glucose status could be, in part, attributed to the hyperosmolar stress it induces on HepG2. Also, hyperosmolar mannitol, owing to its cytotoxic impact, is recommended for further confirmatory studies either as a separate therapeutic or as an adjuvant to sorafenib.

Background: Liver diseases are a common cause of mortality and morbidity over the world. It is caused mainly by toxic chemicals and chemotherapeutic agents. Costus speciosus (Koen ex. Retz.) (Zingiberaceae) is widely employed in various traditional medicines for the prevention and treatment of different aliments. The purpose of this study is to assess the protective effect of C. speciosus rhizomes MeOH extract against the injury of the liver induced by paracetamol (PA) in mice. Material and Methods: The mice were pretreated for seven days with distilled H2O, silymarin 12 mg/kg or 100 and 200 mg/kg MeOH extract. Then, PA (750 mg/kg) was also intra-peritoneal administrated once a day. Animals were euthanatized 24 h after the damage inducement. The levels of the serum enzymes aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase, in addition to the tumor necrosis factor-alpha (TNF-α), were determined. Moreover, the histopathological examination was carried out. Results: Administration of the MeOH extract (200 mg/kg) showed improvement in the toxic effects of PA through significant fall on the serum markers enzymes of liver damage: AST, ALT, and ALP, as well as TNF-α, compared to silymarin. In parallel, the histopathological profile in the mice` liver also proved that extract markedly minimized the PA toxicity and maintained the liver tissues` histoarchitecture to near the normal ones more than that achieved by silymarin. Conclusion: The findings suggested that C. speciosus extract acts as a potential hepatoprotective agent against PA-induced liver toxicity. This hepato-protection effect may be due to the existence of steroids, saponins, different glycosides, and phenolic compounds in C. speciosus.

Garcinia mangostana L. (the queen of fruits, mangosteen, family Guttiferae) is a wealthy source of xanthones. The CHCl3 soluble fraction of the air-dried pericarps of G. mangostana provided a new xanthone: mangostanaxanthone VII (5), along with four known xanthones: mangostanaxanthones I (1) and II (2), gartanin (3) and γ-mangostin (4). The structural verification of these metabolites was achieved by different spectral techniques, including UV, IR, 1D and 2D NMR and HRESIMS. The new metabolite was assessed for cytotoxic potential, using sulforhodamine B (SRB) assay towards the A549 and MCF-7 cancer cell lines. Moreover, its antimicrobial effects were evaluated against various bacterial and fungal strains, using agar disc diffusion assay. Mangostanaxanthone VII showed moderate cytotoxic activity against the A549 and MCF7 cell lines with IC50s 26.1 and 34.8 μM, respectively, compared with doxorubicin (0.74 and 0.41 μM, respectively).

This study targeted to test the potential protective role of lutein against lung and liver damage associated with cyclophosphamide (CP) administration. Lutein was given orally for 5days at two different doses both before and after CP injection. Results have shown that CP administration caused marked pulmonary and hepatic injurious effects in mice. Lung damage was evident through increased lung wet/dry ratio, elevated inflammatory cells infiltration into the pulmonary tissues, increased total protein content and lactate dehydrogenase (LDH) activity in the broncho-alveolar lavage fluid. Estimation of high levels of serum transaminases, alkaline phosphatase and LDH in serum revealed hepatic injury. Histopathological examination of both organs confirmed the biochemical analysis. Elevation of oxidative stress along with depressed anti-oxidant status of lung and liver were evident in CP-intoxicated animals. Furthermore, CP induced elevation of inflammatory cytokines (NOx, TNF-α, IL-6) contaminant with activation of nuclear factor kappa-B (NF-κB) and p38 mitogen activated protein kinase (p38-MAPK). On the other side, lutein treatment successfully protected the lung and the liver as indicated by improvement of the biochemical and histopathological parameters. These results suggest that lutein can ameliorate CP-induced pulmonary and hepatic oxidative injurious effects via inhibition of reactive oxygen species (ROS)/NF-κB/MAPK pathway.

Context The immune system plays a significant role in controlling carcinogenesis, even though most cancers escape immune surveillance through a variety of mechanisms. Objective The aim of the present study was to evaluate the prognostic significance of the novel co-inhibitory B and T lymphocyte attenuator (BTLA) in acute myeloid leukemia (AML) patients as well as its correlation with immune cell populations and treatment outcomes. Design And Setting We conducted case control study on de novo AML patients recruited from Internal Medicine Department, Clinical Hematology and Stem Cell Transplantation Unit, Ain Shams University Hospitals, Cairo, Egypt. The study was held from November 2018 to February 2019 with one year follow up of enrolled cases. Patients and Participants A total of 60 newly diagnosed AML patients and 15 healthy controls were recruited. Interventions We investigated mRNA expression of (BTLA) on peripheral blood in AML patients, and age and sex matched healthy control. Results BTLA expression was significantly up-regulated in patients in comparison to controls (p = 0.024). The expression level of BTLA in CD13+, CD33+, HLA-DR+ patients was significantly higher than in CD13- (p = 0.003), CD33- (p Conclusions These findings provide a basis for the concept that BTLA up-regulation is involved in inhibition of antitumor immunity, and that high BTLA expression level could be considered an independent biomarker for poor prognosis and survival of AML patients.

Introduction Provided the physiologic tumor suppressive role a healthy immune system has, diagnosis of cancer is sometimes also regarded as a diagnosis of an immune dysfunction. Immunoediting refers to the change of immune system response from tumor protection to tumor promotion, favoring the growth of poorly immunogenic clones that have the ability to evade the immune response. Among the mechanisms by which the tumor cells bypass the immune system is immune checkpoints. Which are immune inhibitory pathways responsible for self-tolerance and limiting self-tissue damage by controlling the magnitude and duration of the immune reaction. Objective Studying the expression of the novel immune checkpoint BTLA in patients with AML and evaluate its clinicopathological and diagnostic significance. Patients and methods We investigated the expression of BTLA gene in 60 AML cases and 15 healthy controls using RT-PCR. Results The current study revealed that significant up regulation of BTLA mRNA expression in AML patients as in comparison with the control group (P=0.024). Discussion These results provide a basis for the perception that BTLA upregulation is involved in inhibition of antitumor immunity and that high BTLA expression level can be made use of as a diagnostic marker in patients with AML.

A new peroxy fatty acid, tagetnoic acid (

Cyperus rotundus L. (Suada, Sueda, family: Cyperaceae) is vastly spread in several world's subtropical and tropical regions. It had variable traditional uses and bioactivities. A new flavonol derivative: cyperaflavoside (myricetin 3,3′,5′-trimethyl ether 7-O-β-d-glucopyranoside) and five flavonoids: vitexin, orientin, cinaroside, quercetin 3-O-β-d-glucopyranoside, and myrcetin 3-O-β-d-glucopyranoside were separated from the methanolic extract of C. rotundus aerial parts. Their structures were verified based on UV, IR, NMR (1D and 2D), HRESIMS, and comparison with literature. All metabolites were assessed for their 5-lipoxygenase inhibitory potential. All compounds possessed 5-lipoxygenase inhibitory potentials with IC50s 5.1, 4.5, 5.9, 4.0, 3.7, and 2.3 μM, respectively, in comparison to indomethacin (IC50 0.98 μM). These results supported the traditional uses of C. rotundus in treating inflammation and its related symptoms. Keywords: Cyperaceae, Flavonols, Myricetin derivative, 5-Lipoxygenase inhibitor, Inflammation, Structural activity relationship

Fungi produce a wide range of structurally unique metabolites. Depsidones represent one of the most interesting classes of metabolites, consisting of two 2,4-dihydroxybenzoic acid rings linked together by both ether and ester bonds. Naturally occurring depsidones are produced by lichen, fungi, and plants. They possessed a wide array of bioactivities, including antioxidant, antiproliferative, antimalarial, cytotoxic, antibacterial, radical scavenging, antihypertensive, anti-inflammatory, antifungal, and aromatase and protein kinase inhibitory. In order to point out the potential of this class of compounds, the present review focuses only on the depsidones that have been isolated from fungal source and published from 1978 to 2018. This review outlined the research on the biosynthesis, source, isolation, spectral and physical data, and bioactivities of the naturally occurring fungal depsidones. On the basis of 88 references, > 80 compounds have been described.

A new prenylated xanthone, garcixanthone A (5), together with eight known compounds, mangostanaxanthones I (1) and II (2), garcinone E (3), β-mangostin (4), 8-hydroxycudraxanthone G (6), garcinone C (7), cudraxanthone G (8), and (-)-epicatechin (9) were isolated from the EtOAc-soluble fraction of the air-dried pericarps of Garcinia mangostana (family Clusiaceae). Their structures were verified on the basis of spectroscopic data interpretation as well as comparison with the literature. The cytotoxic and antimicrobial activities of the new compound were assessed using sulforhodamine B (SRB) and agar disk diffusion assays, respectively. Compound 5 showed significant cytotoxic potential against epithelial lung carcinoma (A549) and breast carcinoma (MCF7) cell lines with IC50s 3.0 and 4.2 μM, respectively, compared to doxorubicin (0.74 and 0.41 μM, respectively).

Fusarithioamide B (6), a new aminobenzamide derivative with unprecedented carbon skeleton and five known metabolites: stigmast-4-ene-3-one (1), stigmasta-4,6,8(14),22-tetraen-3-one (2), p-hydroxyacetophenone (3), tyrosol (4), and fusarithioamide A (5) were separated from Fusarium chlamydosporium EtOAc extract isolated from Anvillea garcinii (Burm.f.) DC. leaves (Asteraceae). The structure elucidation and complete assignment of the isolated metabolites were performed mainly by the aid of various NMR and MS data. Fusarithioamide B (6) has been assessed for antibacterial and antifungal activities towards various microbial strains by disc diffusion assay. It exhibited selective antifungal activity towards C. albicans (MIC 1.9 µg/ml and IZD 14.5 mm), comparing to clotrimazole (MIC 2.8 µg/ml and IZD 17.9 mm). Also, it possessed high antibacterial potential towards E. coli, B. cereus, and S. aureus compared to ciprofloxacin. Furthermore, 6 was tested for the in vitro cytotoxic effect against KB, HCT-116, BT-549, MCF-7, SKOV-3, and SK-MEL cell lines. It had selective and potent effect towards BT-549, MCF-7, SKOV-3, and HCT-116 cell lines with IC50s 0.09, 0.21, 1.23, and 0.59 μM, respectively compared to doxorubicin (IC50s 0.046, 0.05, 0.321, and 0.24 μM, respectively). Fusarithioamide B may provide a lead molecule for future developing of antitumor and antimicrobial agents.

Background: Endophytic fungi attracted attention as a prolific source of bioactive natural products with a potent pharmaceutical activity and unique structure. Objective: The main goal of the study is to separate and identify the bioactive constituents from the endophytic fungus Fusarium sp. as well as to evaluate the antimicrobial of the new metabolites. Materials and Methods: The fungus was cultured on a rice medium, and then, the cultures were extracted with ethyl acetate (EtOAc). The EtOAc extract was chromatographed utilizing different chromatographic methods to give five metabolites. The structural determination of these metabolites was carried out by the analyses of various spectroscopic data, in addition to comparison with the formerly reported data. The antifungal and antibacterial potentials were evaluated toward various microbial strains using disc diffusion assay. Results: A new aminobenzamide derivative, namely fusaribenzamide A (2), and four known metabolites: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), adenosine (3), p-hydroxyacetophenone (4), and tyrosol (5) were isolated. Fusaribenzamide A (2) possessed significant antifungal activity toward Candida albicans with minimum inhibitory concentration (MIC) value 11.9 μg/disc compared to nystatin (MIC 4.9 μg/disc). Conclusion: The endophytic fungus Fusarium sp. could be considered as a wealthy pool for the isolation of aminobenzamide derivatives. Fusaribenzamide A may be a candidate for the discovery of a promising antifungal agent. Abbreviations Used: CC: Column chromatography; CHCl3: Chloroform; COSY: Correlations spectroscopy; DBE: double bond equivalent; EtOAc: Ethyl acetate; DMSO: Dimethyl sulfoxide; H2SO4: Sulfuric acid; HMBC: Heteronuclear multiple bond correlation experiment; HRMS: High-resolution mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; HSQC: Heteronuclear single quantum correlation; IR: Infrared; IZD: Inhibition zone diameter; KBr: Potassium bromide; LTQ: Linear trap quadrupole; MeOH; Methanol; MIC: Minimum inhibitory concentration; NMR: Nuclear magnetic resonance; RP: Reversed phase; SiO2: Silica gel; TLC: Thin-layer chromatography; UV: Ultraviolet; VLC: Vacuum liquid chromatography.

Background: Marine organisms are established to be a wealthy source of bioactive compounds with diverse chemical structures and bioactivities. Acanthostrongylophora ingens is known to be rich with pyrimidine b-carboline and manzamine-type alkaloids. The goal of the present work is to isolate and identify new alkaloids from A. ingens as well as to assess the cytotoxic potential of these metabolites towards various cancer cell lines. Methods: The crude MeOH extract of the sponge was separated by vacuum liquid chromatography (VLC), using n-hexane, EtOAc, and MeOH. The EtOAc fraction was chromatographed on VLC, SiO2, sephadex LH-20, and RP18columns, affording four metabolites. Their structures were identified using infrared, ultraviolet, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopic techniques, as well as comparison with the published data. Results: A new 1,2,3,4-tetrahydro-β-carboline (THβCs) alkaloid, ingenine F (4) and three known compounds: Annomontine (1), acanthomine A (2), and 1-oxo-1,2,3,4-THβCs (3) were isolated and identified. Ingenine F (4) exhibited cytotoxic activity toward hormone-dependent breast carcinoma (MCF7), colon carcinoma (HCT116), and lung carcinoma (A549) cell lines with IC50 values of 2.82, 1.00, and 2.37 μM, respectively, compared to doxorubicin (IC50 0.012, 0.036, and 0.102 μM, respectively). Conclusion: It is thefirst report for the isolation of THβCs alkaloids from A. ingens. The THβCs alkaloid with N-methylbutyramide unit as found in ingenine F is very rarely encountered in nature. Ingenine F may provide new promising candidates for potential cytotoxic agent. Abbreviations used: 1D: One-dimensional; 2D: Two-dimensional; CC: Column chromatography; COSY: Correlations spectroscopy; DMSO: Dimethyl sulfoxide; HMBC: Heteronuclear multiple bond correlation experiment; HRESIMS: High resolution electrospray ionization mass spectrometry; HSQC: Heteronuclear single quantum correlation; IR: Infrared; LCQ: Liquid chromatography quadrupole; LTQ: Linear trap quadropole; NMR: Nuclear magnetic resonance; RP: Reversed phase; SiO2: Silica gel; TLC: Thin-layer chromatography; UV: Ultraviolet; VLC: Vacuum liquid chromatography.

Background: Endophytic fungi are of a growing interest as prominent sources of structurally unique bioactive natural products. Objective: This study aims to isolate and characterize bio-metabolites from the endophytic fungus Fusarium sp. isolated from Mentha longifolia L. roots as well as to assess the antimicrobial and cytotoxic potential of these metabolites. Materials and Methods: The endophytic fungi Fusarium sp. was cultured on a rice medium. The rice cultures' ethyl acetate extract was separated using various chromatographic techniques (SiO2, RP-18, and sephadex LH-20) to afford four metabolites. Their structural characterization was achieved by various spectroscopic analyses, as well as comparing with the published data. Results: A new ergosterol derivative namely, fusaristerol A (22E,24R-5β,8β-epidioxyergosta-22-en-3β-yl decanoate) (1), along with ergosta-7,22-diene-3β,5α,6β-triol (2), ergosta-5,7,22-triene-3β-ol (3), and (22E,24R)-ergosta-7,22-dien-3β-ol (4), was separated. Fusaristerol A (1) possessed a significant antifungal activity toward Candida albicans with minimum inhibitory concentration (MIC) value of 8.3 μg/disc compared to clotrimazole (MIC 5.1 μg/disc). Moreover, it displayed a potent cytotoxic potential toward HCT-116 cell line with an half maximal inhibitory concentration (IC50) value of 0.21 μM, compared to doxorubicin (IC50 0.06 μM). Conclusion: This is the first report for separation of a 5,8-epidioxy ergostane derivative from Fusarium sp. Fusaristerol A may provide a new promising candidate for the development of a potential anti-candida and cytotoxic agent. Abbreviations used: BT-549: Ductal carcinoma; CC: Column chromatography; COSY: Correlations spectroscopy; CDCl3: Deuterated chloroform; EtOAc: Ethyl acetate; DMSO: Dimethyl sulfoxide; EIMS; Electron-impact mass spectrometry; EP: Ergosterol peroxide; GCMS; Gas chromatography mass spectrometry; HCl: Hydrochloric acid; H2O: Water; H2SO4: Sulfuric acid; HMBC: Heteronuclear multiple bond correlation experiment; HRMS: High-resolution mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; HCT-116: Colorectal adenocarcinoma; HSQC: Heteronuclear single-quantum correlation; IC50: Half maximal inhibitory concentration; IR: Infrared; KBr: Potassium bromide; KOH; Potassium hydroxide; LTQ: Linear trap quadruple; MeOH; Methanol; MIC: Minimum inhibitory concentration; MCF-7: Human breast adenocarcinoma; NMR: Nuclear magnetic resonance; PDA: Potato dextrose agar; RP: Reversed phase; SiO2: Silica gel; TLC: Thin-layer chromatography; VLC: Vacuum liquid chromatography.