Sabrin R.M. Ibrahim

Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa.

Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D (1H, 13C and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the template for ring closure and afforded the linkage to the peptidic side chain which was always initiated with a proline moiety. All peptides contained three or more proline residues and the remaining residues were predominantly hydrophobic residues with all amino acids present in the l form. Callyaerins A-F (1-6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 microM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.

Mangostanaxanthones I and II, new xanthones from the pericarp of Garcinia mangostana.

Two new xanthones: mangostanaxanthones I (3) and II (5) were isolated from the pericarp of Garcinia mangostana, along with four known xanthones: 9-hydroxycalabaxanthone (1), parvifolixanthone C (2), α-mangostin (4), and rubraxanthone (6). Their structures were elucidated on the basis of IR, UV, 1D, 2D NMR, and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their antioxidant, antimicrobial, and quorum-sensing inhibitory activities. Compounds 3 and 5 displayed promising antioxidant activity with IC50 12.07 and 14.12 μM, respectively using DPPH assay. Compounds 4-6 had weak to moderate activity against Escherichia coli and Staphylococcus aureus, while demonstrated promising action against Bacillus cereus with MICs 0.25, 1.0, and 1.0mg/mL, respectively. The tested compounds were inactive against Candida albicans. However, they showed selective antifungal potential toward Aspergillus fumigatus. Compounds 3 and 4 possessed quorum-sensing inhibitory activity against Chromobacterium violaceum ATCC 12472.

Portulene, a new diterpene from Portulaca oleracea L.

Chromatographic fractionation of the chloroform extract of Portulaca oleracea L. growing in Egypt afforded a new clerodene diterpene portulene (1), in addition to the known compounds lupeol (2), β-sitosterol (3), and daucosterol (4), which were reported for the first time from the title plant. The structures of the isolated compounds were unambiguously established through 1D, 2D, and mass spectral analyses. Co-treatment of CCl4 hepatic injured rats with 70% alcohol extract of P. oleracea significantly restored the hepatic marker enzymes and total bilirubin to near-normal values, which demonstrated hepatoprotective activity. In addition, the P. oleracea extract showed antibacterial and antifungal activities.

Litchi chinensis: medicinal uses, phytochemistry, and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE Litchi chinensis Sonn. (Sapindaceae) has been widely used in many cultures for the treatment of cough, flatulence, stomach ulcers, diabetes, obesity, testicular swelling, hernia-like conditions, and epigastric and neuralgic pains. The ethnopharmacologial history of L. chinensis indicated that it possesses hypoglycemic, anticancer, antibacterial, anti-hyperlipidemic, anti-platelet, anti-tussive, analgesic, antipyretic, hemostatic, diuretic, and antiviral activities. AIM OF THE REVIEW The aim of this review is to provide up-to-date information on the botanical characterization, distribution, traditional uses, and chemical constituents, as well as the pharmacological activities and toxicity of L. chinensis. Moreover, the focus of this review is the possible exploitation of this plant to treat different diseases and to suggest future investigations. MATERIALS AND METHODS To provide an overview of the ethnopharmacology, chemical constituents, and pharmacological activities of litchi, and to reveal their therapeutic potentials and being an evidence base for further research works, information on litchi was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search (PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library, and pubs.acs.org/journal/jacsat). All abstracts and full-text articles were examined. The most relevant articles were selected for screening and inclusion in this review. RESULTS A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethno-medical uses of L. chinensis have been recorded in China, India, Vietnam, Indonesia, and Philippines. Phytochemical investigation revealed that the major chemical constituents of litchi are flavonoids, sterols, triterpenens, phenolics, and other bioactive compounds. Crude extracts and pure compounds isolated from L. chinensis exhibited significant antioxidant, anti-cancer, anti-inflammatory, anti-microbial, anti-viral, anti-diabetic, anti-obesity, hepato-protective, and immunomodulatory activities. From the toxicological perspective, litchi fruit juice and extracts have been proven to be safe at a dose 1 g/kg. CONCLUSIONS Phytochemical investigations indicated that phenolics were the major bioactive components of L. chinensis with potential pharmacological activities. The ethnopharmacological relevance of L. chinensis is fully justified by the most recent findings indicating it is a useful medicinal and nutritional agent for treating a wide range of human disorders and aliments. Further investigations are needed to fully understand the mode of action of the active constituents and to fully exploit its preventive and therapeutic potentials.

Naphthylisoquinoline alkaloids potential drug leads.

Naphthylisoquinolines are a group of structurally diverse secondary metabolites, consisting of naphthalene and isoquinoline moieties. Naturally occurring naphthylisoquinolines have so far been found only in the small palaeotropic families Dioncophyllaceae and Ancistrocladaceae. They have been shown to exhibit a diverse array of biological activities. Herein, we review the research on the occurrence, isolation, identification, biological activities, and biosynthesis of this class of compounds published from 1995 till now. Moreover, their chemotaxonomic relevance and molecular targets of action have been discussed. More than 125 metabolites are described and 99 references are cited.

Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei.

In our search for bioactive metabolites from marine organisms, we have investigated the polar fraction of the organic extract of the Red Sea sponge Theonella swinhoei. Successive chromatographic separations and final HPLC purification of the potent antifungal fraction afforded a new bicyclic glycopeptide, theonellamide G (1). The structure of the peptide was determined using extensive 1D and 2D NMR and high-resolution mass spectral determinations. The absolute configuration of theonellamide G was determined by chemical degradation and 2D NMR spectroscopy. Theonellamide G showed potent antifungal activity towards wild and amphotericin B-resistant strains of Candida albicans with IC50 of 4.49 and 2.0 μM, respectively. Additionally, it displayed cytotoxic activity against the human colon adenocarcinoma cell line (HCT-16) with IC50 of 6.0 μM. These findings provide further insight into the chemical diversity and biological activities of this class of compounds.

Lupeol-3-O-decanoate, a new triterpene ester from Cadaba farinosa Forssk. growing in Saudi Arabia

A new triterpene ester (1) together with eight known compounds (2–9) were isolated from the leaves of Cadaba farinosa Forssk. Their chemical structures were established on the basis of physical, chemical, and spectroscopic methods (IR, 1D and 2D NMR, and mass spectral analyses) to be: lupeol-3-O-decanoate (1), lupeol (2), β-sitosterol (3), ursolic acid (4), 12-aminododecanoic (5), dillenetin-3-O-β-d-glucopyranoside (6), stachydrine (7), 3-hydroxy-stachydrine (8), and quercetin-3-O-β-d-glucopyranoside (9). That is the first report for the isolation of compound 5 from a plant source. Compounds 5, 6, and 9 were evaluated for their antioxidant activity.

Terrenolide S, a new antileishmanial butenolide from the endophytic fungus Aspergillus terreus

Abstract Terrenolide S, a new butenolide derivative (6), together with six known compounds: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), stigmasta-4,6,8(14),22-tetraen-3-one (3), terretonin A (4), terretonin (5) and butyrolactone VI (7) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were established by extensive spectroscopic analyses (1D, 2D NMR and HRESIMS), as well as optical rotation measurement and comparison with literature data. Compound 1 displayed a potent activity towards methicillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans with IC50 values of 2.29 and 10.68 µM, respectively. Moreover, 1, 2 and 6 exhibited antileishmanial activity towards Leishmania donovani with IC50 values of 11.24, 15.32 and 27.27 µM, respectively and IC90 values of 14.68, 40.56 and 167.03 µM, respectively. Graphical Abstract

New anti-inflammatory flavonoids from Cadaba glandulosa Forssk

Three new flavonoids; kaempferol-4′-phenoxy-3,3′,5′-trimethylether (3), rhamnocitrin-4′-(4-hydroxy-3-methoxy)phenoxy-3-methyl ether (4), and rhamnocitrin-3-O-neohesperoside-4′-O-rhamnoside (6), along with three known compounds; 4-methoxy-benzyldehyde (1), kaempferol-3-methylether (2), and stachydrine (5) were isolated from the aerial parts of Cadaba glandulosa Forssk. Their chemical structures were established by physical, chemical, and spectral methods, as well as comparison with literature data. The antioxidant and anti-inflammatory activities of the isolated compounds were determined. Compounds 2–4, and 6 exhibited potent anti-inflammatory activity comparable with indomethacin and moderate antioxidant activity.

New xanthones and cytotoxic constituents from Garcinia mangostana fruit hulls against human hepatocellular, breast, and colorectal cancer cell lines

ETHNOPHARMACOLOGICAL RELEVANCE Cancer has proceeded to surpass one of the most chronic illnesses to be the major cause of mortality in both the developing and developed world. Garcinia mangostana L. (mangosteen, family Guttiferae) known as the queen of fruits, is one of the most popular tropical fruits. It is cultivated in Southeast Asian countries: Malaysia, Indonesia, Sri Lanka, Burma, Thailand, and Philippines. Traditionally, numerous parts of G. mangostana have been utilized to treat various ailments such as abdominal pain, haemorrhoids, food allergies, arthritis, leucorrhoea, gonorrhea, diarrhea, dysentery, wound infection, suppuration, and chronic ulcer. AIM OF STUDY Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated. MATERIALS AND METHODS The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry. RESULTS The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50s ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50s ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells. CONCLUSION Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.