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SARS-CoV-2, the new coronavirus variant is a world-wide health crisis. Over spans of human history, preparations derived from natural products have always been recognized as a preliminary source of medications. Taking into account the SARS-CoV-2 main protease (Mpro) as the essential element of the viral cycle and as a main target, herein we highlight a computer-aided comprehensive virtual screening for a focused chemical list of 14 laulimalides marine macrolides against SARS-CoV-2 main protease (Mpro) using a set of integrated modern computational techniques including molecular docking (MDock), molecule dynamic simulations (MDS) and structure-activity relationships (SARs) as well. Indeed, computational studies had disclosed two promising macrolides [laulimalides LA4 (6) and LA18 (13)] based on their remarkable ligand-protein energy scores and relevant binding affinities with the SARS-CoV-2 (Mpro) pocket residues. Consequentially, the two compounds were further investigated thermodynamically though deciphering their MD simulations at 100 ns, where they showed noticeable stability within the accommodated (Mpro) pockets. Moreover, in-deep SARs studies suggested the crucial roles of the C-23 subistituted side chain and the C-20 methoxy as essential pharmacophoric structural features for activity. Such interesting outcomes are highly recommending further in vitro/vivo examinations regarding those marine macrolides and open a gate towards developing more effective antivirals drug leads.

Microorganisms still remain as main hotspots in the global drug discovery avenue. In particular, fungi are highly prolific producers of a vast of structurally divers specialised secondary metabolites, which have displayed a myriad of biomedical potentialities. Intriguingly, isocoumarins is one distinctive class of fungal natural products polyketides, which demonstrated numerous remarkable biological and pharmacological activities. This review article provides a comprehensive state of the art over the period 2000-2022 about the discovery, isolation, classifications, and therapeutic potentialities of isocoumarins exclusively reported from fungi. Indeed, a comprehensive list of 351 structurally diverse isocoumarins were documented, classified according to their fungal sources [16 order/ 28 family/ 55 genera] where they have been originally discovered, alongside, their reported pharmacological activities wherever applicable. Also, recent insights around their proposed and experimentally proven biosynthetic pathways are also briefly discussed.

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.

Pachira glabra is a medium sized tree that is famous for its delicious edible seeds and leaves. Phytochemical investigation of Pachira glabra leaf alcohol extract led to the isolation of a new γ-pyrone glycoside, 7-hydroxy maltol-3-O-β-d-glucoside (HMGlu). In vivo assessment of the gastro-protective activity of HMGlu demonstrated superior gastro-protection at a dose of 100 mg kg-1, close to the value triggered by the standard reference omeprazole drug (evidenced by morphological and histopathological examinations). This was further confirmed by immunohistochemical staining where pretreatment with HMGlu (100 mg kg-1) markedly reduced NFκB, COX-2 and BAX positively-stained cells. Thus, it can be concluded that 7-hydroxy maltol-3-O-β-d-glucoside can be a new pharmaceutically active agent with promising gastro-protective activity of natural origin.

Phytochemical investigations of Bombacoideae resulted in the identification of almost 160 secondary metabolites belonging to various chemical classes, including flavonoids, lignans, procyanidinds, naphthoquinones, sesquiterpenes, and triterpenes. This chapter sheds light on the recently isolated constituents, as well as the pharmacological activities of different genera of this medicinally valuable Bombacoideae. Flavonoids constituted the most prevailing class of secondary metabolites, representing 27% of total isolated compounds, followed by sesquiterpenes and fatty acids. Inhibition of nitric oxide synthase, cyclooxygenases, and pro-inflammatory cytokines, together with the antioxidant potentials were the major mechanisms adopted by the most-studied Bombacoideae members and their isolated compounds. The anti-inflammatory potential was most commonly ascribed to the flavonoid content and to a lesser extent to other metabolites, such as fatty acids, despite the possibility of contribution of other reported secondary metabolites having anti-inflammatory potential, such as tannins and triterpenes. Major compound classes identified include naphthoquinone derivatives, flavonoids, coumarins, sesquiterpenes, and triterpenes.

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.

The leaves and stems of the two Pachira species cultivated in Egypt, namely Pachira aquatica, and Pachira glabra were qualitatively and quantitatively examined for their volatile constituents emplo...

The chemical composition, pharmacological activity and traditional uses of 20 species attributed to the genus Enterolobium (Fabaceae) as used in the South and Central America, and Tropical Africa, were revised and compared. A survey of the available literature shows that these species are used mostly for their anti-inflammatory and cytotoxic activities. Additionally, some of these Enterolobium species showed antibacterial, antifungal, insecticidal, molluscicidal and larvicidal activities. Generally, the triterpenes or the phenolic compounds isolated from these plant extracts are assumed to be the bioactive principles.

Aims: The present study aimed to evaluate the cytotoxic activities of the aqueous alcohol extract of Enterolobium timbouva leaves as well as its isolated pure compounds. Place and Duration of Study: Department of Pharmacognosy, Faculty of pharmacy, Ain Shams University, between March 2010 and May 2012. Methodology: In vitro Cytotoxic study was conducted for the aqueous methanol extract and the isolated pure single compounds to determine the IC50 by sulphorhodamine B (SRB) assay. Results: Phytochemical investigation of the extract resulted in the isolation and structural determination of ten phenolic compounds isolated for the first time from entitled genus viz; 3,4-Dihydroxy-Cinnamic acid (Caffeic acid) (1); Quercetin-3-O-β-D-glucopyranoside (Isoquercitrin) (2); Quercetin-3-O-β-D-galacto-pyranoside (Hyperin) (3); Kaempferol-3-O-β-D–glucopyranoside (Astragalin) (4); Hesperetin-7-O-rutinoside (Hesperidin) (5); Quercetin 3-O-rutinoside (Rutin) (6); Quercetin (7); Kaempferol (8); 7-methoxycoumarin (Herniarin) (9); and Chrysin (10). The aqueous alcohol extract exhibited potent cytotoxic activity against diffferent cancer cell lines with IC50 values of 2.67 μg/mL against MCF-7 cell line, 3.89 μg/ml against HCT116 cells, 4 μg/mL against HEp2 cells, 4.5 μg/mL against HeLa cells, 1.7 μg/mL against PC-3 cells, and 5.7 μg/mL against Huh-7 cells. In vitro cytotoxic assay of the isolated pure compounds against Huh-7 cell Line showed that compounds 1, 9 and 10 are the only tested compounds exhibiting potent cytotoxic activity with IC50 of 3 μg/mL, 0.76 μg/mL, and 18.51 μg/mL respectively. The rest of tested compounds exhibited IC50 exceeding 1000 μg/mL which reflects their safety. Conclusion: The current study indicated that the phenolic compounds isolated from Enterolobium timbouva leaves are promising molecules with potentially useful cytotoxic activity profiles. This confirms that this terrestrial plant has great value as a source of lead compounds with pharmaceutical applications.