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Recently, it has been shown that metabolites derived from endosymbiotic fungi attracted high attention, since plenty of them have promising pharmaceutical applications. The variation of metabolic pathways in fungi is considered an optimistic source for lead compounds. Among these classes are terpenoids, alkaloids, polyketides, and steroids, which have proved several pharmacological activities, including antitumor, antimicrobial, anti-inflammatory, and antiviral actions. This review concludes the major isolated compounds from different strains of Penicillium chrysogenum during the period 2013–2023, together with their reported pharmacological activities. From literature surveys, 277 compounds have been identified from P. chrysogenum, which has been isolated as an endosymbiotic fungus from different host organisms, with specific attention paid to those showing marked biological activities that could be useful in the pharmaceutical industry in the future. This review represents documentation for a valuable reference for promising pharmaceutical applications or further needed studies on P. chrysogenum.

Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against α-glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human α-glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC50 values of 40.89 µg/mL and 97.97 µg/mL, respectively (Trolox IC50 value was 14.59 µg/mL). Moreover, IPR-J and IPR-E exhibited promising α-glucosidase inhibitory activity displaying IC50 values of 18.52 µg/mL, 57.89 µg/mL, respectively being more potent as compared to acarbose with IC50 value of 362.088 µg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC50 values of 2.35, 4.81, 2.22 and 0.42 µg/mL, respectively compared to cetilistat with IC50 value of 7.47 µg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 µg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human α-glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals.

Aspergillus terreus microorganism represents a promising prospective source for drug discovery since it is rich in diverse kinds of bioactive secondary metabolites. It contributed to many biotechnological applications and its metabolites are used in the synthesis of certain pharmaceuticals and food products, in addition to its useful uses in fermentation processes. There are about 346 compounds identified from marine and terrestrial-derived A. terreus from 1987 until 2022, 172 compounds of them proved a vast array of bioactivity. This review aimed to create an up-to-date comprehensive literature data of A. terreus’s secondary metabolites classes supported by its different bioactivity data to be a scientific record for the next work in drug discovery.

Bontia daphnoides L. has been utilized in traditional medicine for treatment of herpes, cough and colds. The aim of this study was to analyze the volatile constituents of this plant by GC/MS (Gas Chromatography coupled to Mass Spectrometry) and to assess their antiviral activity. A total of 64 compounds were identified where dehydroepingaione represented 83.60, 72.36, 58.78 and 34.18% in the leaves, stems, flowers and fruits, respectively. Principal component and hierarchical cluster analysis revealed the discrimination of the organs as the leaves and stems were distributed in the same cluster in contrast to the flowers and fruits. Furthermore, the antiviral activity was assessed where the oils of leaves and stems exhibited potent antiviral activity displaying IC50 of 11.98, 12.62 µg/ml against HSV-1 and 13.34, 14.50 µg/ml against CoxB4, respectively. Dehydroepingaione was isolated from the n-hexane fraction of the leaves and showed activity against HSV-1 and CoxB with IC50 of 24.46 and 25.32 µg/ml, respectively. Molecular modelling studies illustrated that the major compounds showed good affinity towards HSV type-1 thymidine kinase. Therefore, it can be concluded that the oils from B. daphnoides have promising antiviral activity that may be attributed to the major oxygenated sesquiterpenes.

Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1′''-6′')-(4′'- O -acetyl)-β -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3′-O-β-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1′''-6′')-(4′'- O -acetyl)- β –Dgalactoside (4), quercetin-3- O—β -D-galactoside (5), 7-hydroxy maltol-3-O-β-D-glucoside (6), maltol-3- O-β -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.

This study aimed to investigate the antiproliferative effect of aqueous and organic extracts of mulberry leaves (Morus Alba L.) on human hepatocellular carcinoma HepG2 cell line. Mulberry leaf extracts were prepared using the solvents: water, 50% aqueous MeOH, and 100% MeOH for different time intervals, while the cells treated with dimethyl sulfoxide (DMSO) served as control. The effects of aqueous and organic extracts of M. alba L. leaves on HepG2 cell viability, nuclear factor kappa B (NF-jB) gene expression, alfa-fetoprotein (AFP), albumin (ALB), gamma- glutamyl transpeptidase (c-GT) and alkaline phosphatase (ALP) were measured. The results of the cell viability assays showed that water, 50% aqueous MeOH, and 100% MeOH extracts exhibited a highly significant inhibitory effect on HepG2 cell proliferation which was evidenced by a reduction in viable cell count. The results were confirmed by microscopical examination of cell morphology. Furthermore, the mulberry leaf extracts suppressed the activity of NF-jB gene expression of HepG2 cells compared to the control. Also a highly significant depression occurred at the levels of AFP, c-GT and ALP in HepG2 cells compared with that of controls in a time dependent manner. By contrast, the mulberry leaf extracts increased the secretion of ALB. Therefore, the conclusion was that the organic and aqueous extracts of mulberry leaves inhibit the growth of HepG2 cells through suppressing the activity of NF-jB gene expression and modulate the biochemical markers. � 2013 Production and hosting by Elsevier B.V. on behalf of Ain Shams University.

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in cancer angiogenesis. In this study, a series of novel furo[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine based-derivatives were designed and synthesized as VEGFR-2 inhibitors, in accordance to the structure activity relationship (SAR) studies of known type II VEGFR-2 inhibitors. The synthesized compounds were evaluated for their ability to in vitro inhibit VEGFR-2 kinase enzyme. Seven compounds (15b, 16c, 16e, 21a, 21b, 21c and 21e) demonstrated highly potent dose-related VEGFR-2 inhibition with IC50 values in nanomolar range, of which the thieno[2,3-d]pyrimidine based-derivatives (21b, 21c and 21e) exhibited IC50 values of 33.4, 47.0 and 21 nM respectively. Moreover, furo[2,3-d]pyrimidine-based derivative (15b) showed the strongest inhibition of human umbilical vein endothelial cells (HUVEC) proliferation with 99.5% inhibition at 10 μM concentration. Consistent with our in vitro findings, compounds (21b and 21e) orally administered at 5 and 10 mg/kg/day for 8 consecutive days demonstrated potent anticancer activity in Erhlich ascites carcinoma (EAC) solid tumor murine model. Such compounds blunted angiogenesis in EAC as evidenced by reduced percent microvessel via decreasing VEGFR-2 phosphorylation with subsequent induction of apoptotic machinery. Furthermore, Miles vascular permeability assay confirmed their antiangiogenic effects in vivo. Intriguingly, such compounds showed no obvious toxicity.

A new 12a-dehydrorotenoid 1, 11-dihydroxy-9, 10-methylenedioxy-12a-dehydrorotenoid (1), together with a new isoflavonoid glycoside tectorigenin-7-O-beta-glucosyl-4'-O-beta-glucoside (3), were isolated and identified from the rhizomes of I. spuria (Zeal). In addition, 4 known compounds, tectorigenin (2) tectorigenin-7-O-beta-glucosyl (1 --> 6) glucoside (4), tectoridin (a tectorigenin-7-O-beta-glucoside) (5) and tectorigenin-4'-O-beta-glucoside (6) were isolated and identified for the first time from this plant. The structures of the isolated compounds were determined by spectroscopic methods (UV, IR, 1H, 13C-NMR, DEPT, HMQC, NOESY, and HMBC experiments and MS spectrometry) and by comparison with literature data of known compounds. Compounds 2, 4, 5, and 6 are reported for the first time from this plant through the present study.