Cytotoxic Alkaloids Derived from Marine Sponges: A Comprehensive Review

Marine sponges (porifera) have proved to be a prolific source of unique bioactive secondary metabolites, among which the alkaloids occupy a special place in terms of unprecedented structures and outstanding biological activities. Identification of active cytotoxic alkaloids extracted from marine animals, particularly sponges, is an important strive, due to lack of knowledge on traditional experiential and ethnopharmacology investigations. In this report, a comprehensive survey of demospongian bioactive alkaloids in the range 1987-2020 had been performed with a special emphasis on the potent cytotoxic activity. Different resources and databases had been investigated, including Scifinder (database for the chemical literature) CAS (Chemical Abstract Service) search, web of science, Marin Lit (marine natural products research) database. More than 230 representatives of different classes of alkaloids had been reviewed and classified, different genera belonging to the phylum porifera had been shown to be a prolific source of alkaloidal molecules, including Agelas sp., Suberea sp., Mycale sp., Haliclona sp., Epipolasis sp., Monanchora sp., Crambe sp., Reniera sp., and Xestospongia sp., among others. The sufficient production of alkaloids derived from sponges is a prosperous approach that requires more attention in future studies to consider the constraints regarding the supply of drugs, attained from marine organisms

Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review

Abstract 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

Bioactive Terpenes from Marine-Derived Fungi

Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities

New Adenosine Derivatives from Aizoon canariense L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts

Aizoaceae is a large succulent family characterized by many psychoactive species. Aizoon canariense L., a wild neglected plant traditionally used in gastrointestinal ailments, has been the subject of a limited number of phytochemical and biological studies. Therefore, herein, we investigated the in vitro cytotoxic, antimicrobial, and anticholinesteraseactivity of the aerial parts of A. canariense L. and analyzed the phytochemical compositions of the lipoidal and alkaloidal fractions. Petroleum ether extract showed the presence of behenic and tricosylic acid, while an in-depth investigation of the alkaloidal fraction revealed the identification of new adenine based alkaloids (1–5), which were isolated and identified for the first time from Aizoon canariense L. Their structures were elucidated based on extensive spectroscopic analyses. The alkaloidal extract showed a powerful cytotoxic effect (IC50 14–28 μg/mL), with the best effect against colon carcinoma, followed by liver and breast carcinomas. The alkaloidal extract also had a potent effect against Candida albicans and Escherichia coli, with minimum inhibitory concentrations (MIC) values of 312.5 and 625 µg/mL. The in vitro anticholinesterase activity was potent, with IC50 < 200 ng/mL for the tested extracts compared with 27.29 ± 0.49 ng/mL for tacrine

Antimicrobial activities of metabolites isolated from endophytic Aspergillus flavus of Sarcophyton ehrenbergi supported by in-silico study and NMR spectroscopy

Abstract Background Endophytic Aspergillus species produce countless valuable bioactive secondary metabolites. In the current study, Aspergillus flavus an endophyte from the soft coral Sarcophyton ehrenbergi was chemically explored and the extracted phytoconstituents were subsequently evaluated for antimicrobial activity. This is accomplished by employing nuclear magnetic resonance (NMR) spectroscopy and computational techniques. Additionally, An in vitro anticancer analysis of A. flavus total extract against breast cancer cells (MCF-7) was investigated. Result Six compounds were separated from the crude alcohol extract of the endophytic Aspergillus flavus out of which anhydro-mevalonolactone was reported for the first time. The anti-fungal and anti-Helicobacter pylori properties of two distinct compounds (Scopularides A and B) were assessed. Additionally, computational research was done to identify the binding mechanisms for all compounds. Both the compounds were found to be active against H. pylori with minimum inhibitory concentration (MIC) values ranging from 7.81 to 15.63 µg/ mL as compared with clarithromycin 1.95 µg/ mL. Scopularides A was potent against both Candida albicans and Aspergillus niger with MIC values ranging from 3.9 to 31.25 µg/ mL, while scopularides B only inhibits Candida albicans with MIC value of 15.63 µg/ mL and weak inhibitory activity against A. niger (MIC = 125 µg/ mL). Furthermore, cytotoxic activity showed a significant effect (IC50: 30.46 mg/mL) against MCF-7 cells. Conclusion Our findings report that cytotoxic activity and molecular docking support the antimicrobial activity of Aspergillus flavus, which could be a promising alternative source as a potential antimicrobial agent

Antimicrobial Profile of Actinomycin D Analogs Secreted by Egyptian Desert Streptomyces sp. DH7

Egyptian deserts are an underexplored ecological niche, especially the Sinai Peninsula. In our recent study, we explored this extreme environment and shed light on the bioactive capabilities of desert Actinobacteria isolated from Sinai. Fifty desert Actinobacteria were isolated from the Sinai desert using mineral salt media, basal media, and starch casein media. The filtrate of Streptomyces sp. DH 7 displayed a high inhibitory effect against multidrug-resistant Staphylococcus aureus (MRSA) strains. The 16S rDNA sequencing confirmed that isolate DH7 belongs to the genus Streptomyces. The NJ phylogenetic tree showed relatedness to the Streptomyces flavofuscus strain NRRL B-2594 and Streptomyces pratensis strain ch24. The minimum inhibitory concentrations against MRSA were 16 and 32 μg/μL. Chemical investigation of the ethyl acetate extract of Streptomyces sp. DH7 led to the isolation and purification of natural products 1–4. Structure elucidation of the purified compounds was performed using detailed spectroscopic analysis including 1 and 2D NMR, and ESI-MS spectrometry. To the best of our knowledge, this is the first report for the isolation of compounds 1–4 from a natural source, while synthetic analogs were previously reported in the literature. Compounds 3–4 were identified as actinomycin D analogues and this is the first report for the production of actinomycin D analogs from the Sinai desert with an inhibitory effect against MRSA. We indorse further study for this analog that can develop enhanced antimicrobial activities. We confirm that the desert ecosystems in Egypt are rich sources of antibiotic-producing Actinobacteria

Benzohydrazide as a good precursor for the synthesis of novel bioactive and anti-oxidant 2-phenyl-1,3,4-oxadiazol-aminoacid derivatives: Structural determination, biological and anti-oxidant activity

The synthesis and biological assessment of 2,5-disubstituted-1,3,4-oxadiazole derivatives from benzo hydrazide and amino acids as novel potential antioxidant and antibacterial agents have been reported. The structures of the new compounds were characterized by physicochemical properties and spectral methods. The synthesized compounds were screened for their in vitro antibacterial activity against three Gram-positive bacterial strains, namely Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, Listeria innocua ATCC 33090, and two Gram-negative bacterial strains, namely Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, and antifungal activity against Candida albicans ATCC 10231 in comparison with Amoxicillin, Tetracycline, Gentamicin and Oxacillin as standards. Most of the compounds have excellent efficacy, and some of them, such as 5i, 5g, 5d, 5c, and 5j can inhibit their activity better or very close to that of Amoxicillin, Tetracycline, Gentamicin, Oxacillin used as standards. Compounds 5b and 5i provided good results against L. innocua with inhibition values of IZ = 14 mm and IZ = 22 mm, respectively, while the rest of the compounds and antibiotics were unable to inhibit it. Compounds 5c, 5d, 5g and 5j showed excellent activity against C. albicans with values between 31 mm and 34 mm. These results were better than all the standards used. The MIC value (25 µg/ml) for derivatives 5(c-e), 5g and 5(i-j) against B. cereus represent the best activity of the tested compounds. All the target compounds were also screened for radical scavenging antioxidant activities by DPPH, FRAP, and TAC assays and found to be excellent antioxidant agents. According to the results, it was observed that most derivatives synthesized showed excellent activity with a concentration of 250 µg/ml as an antioxidant agent (76 % < RSA < 95.5 %) which gave an inhibition percentage that was better or very close to that of ascorbic acid and better than BHT

Chemical and Biological Review of Endophytic Fungi Associated with <i>Morus</i> sp. (Moraceae) and In Silico Study of Their Antidiabetic Potential

The chronic nature of diabetes mellitus motivates the quest for novel agents to improve its management. The scarcity and prior uncontrolled utilization of medicinal plants have encouraged researchers to seek new sources of promising compounds. Recently, endophytes have presented as eco-friendly leading sources for bioactive metabolites. This article reviewed the endophytic fungi associated with Morus species and their isolated compounds, in addition to the biological activities tested on their extracts and chemical constituents. The relevant literature was collected from the years 2008–2022 from PubMed and Web of Science databases. Notably, no antidiabetic activity was reported for any of the Morus-associated endophytic fungal extracts or their twenty-one previously isolated compounds. This encouraged us to perform an in silico study on the previously isolated compounds to explore their possible antidiabetic potential. Furthermore, pharmacokinetic and dynamic stability studies were performed on these compounds. Upon molecular docking, Colletotrichalactone A (14) showed a promising antidiabetic activity due to the inhibition of the α-amylase local target and the human sodium-glucose cotransporter 2 (hSGT2) systemic target with safe pharmacokinetic features. These results provide an in silico interpretation of the possible anti-diabetic potential of Morus endophytic metabolites, yet further study is required

Synthesis, characterization, antimicrobial and antioxidant activity of 2- (2′-hydroxyphenyl) -1,3,4-oxadiazolyl-5-amino acid derivatives

The synthesis and biological assessment of 2,5-disubstituted-1,3,4-oxadiazoles derivatives from amino acids as new potential antibacterial and antioxidant agents have been reported. The structures of the new synthesized compounds were characterized based on physicochemical and spectral data UV–Visible, IR, 1HNMR, 13CNMR. All the target compounds were screened for their in vitro antibacterial activity against three Gram-positive bacterial strains, namely Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, Listeria innocua ATCC 33090, and two Gram-negative bacterial strains, namely Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, and antifungal activity against Candida albicans ATCC 10231 in comparison with Amoxicillin, Tetracycline, Gentamicin and Oxacillin. The only compound 1-{(4S)-4-amino-4-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]butyl}guanidine 5e with the amine radical that showed excellent results against all bacteria, particularly against L. innocua (IZ = 12 mm), has excellent antifungal activity (IZ = 32 mm). The compounds 2-[5-(1-amino-3-methylbutyl)-1,3,4-oxadiazol-2-yl]phenol 5b and 2-[5-(pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl]phenol 5j have excellent activities (IZ = 27 and IZ = 28 mm, respectively) against B. cereus and P. aeruginosa. Compounds 2-{5-[(1R)-1-amino-2-sulfanylethyl]-1,3,4-oxadiazol-2-yl}phenol 5c, 2-{5-[(1S)-1-amino-3-(methylsulfanyl)propyl]-1,3,4-oxadiazol-2-yl}phenol 5d with the sulfur radical, 3--[5-(2-3-amino hydroxyphenyl)-1,3,4-oxadiazol-2-yl]propanamide 5g with the amide radical, 5j with the amino radical, and 4-amino-4-[5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl]butanoic acid 5k gave good results against B. cereus, where 19 mm < IZ < 23 mm. We also found that compound 5j has the greatest activity (IZ = 33 mm) against C. albicans, followed by compounds 5e (IZ = 32 mm) and 5b (IZ = 30 mm). The synthesized compounds were also screened for radical scavenging antioxidant activities by DPPH, FRAP, and TAC assays and found to be good antioxidant agents. According to the IC50 values, all compounds demonstrated good to excellent activity, especially 5b and 2-{5-[1-amino-2-(1H-imidazol-4-yl)ethyl]-1,3,4-oxadiazol-2-yl}phenol 5i for DPPH, 5e and 5i for FRAP and methyl 2-hydroxybenzoate 2, 2-{5-[1-amino-2-(1H-indol-3-yl)ethyl]-1,3,4-oxadiazol-2-yl}phenol 5h with the imidazol group and 2-[5-(1,5-diaminopentyl)-1,3,4-oxadiazol-2-yl]phenol 5f with the imidazol group for TAC. All these compounds showed better activity than AA and BHT

New Meroterpenoid Derivatives from the Pomegranate-Derived Endophytic Fungus <i>Talaromyces purpureogenus</i>

In this study, we report the isolation of two new meroterpenoids, miniolutelide D (1) and miniolutelide E (13-epi-miniolutelide C) (2), along with two meroterpenoidal analogues (3 and 4) and two phenolic compounds (5 and 6) from the endophytic fungus Talaromyces purpureogenus derived from Punica granatum fruits. Their structures were elucidated using extensive MS, 1D, and 2D NMR spectroscopic analyses as well as by comparing with data in the literature. The absolute configurations of 1 and 2 were determined using TDDFT-ECD calculations. Antimicrobial activity was evaluated. Compound 5 displayed significant activity against methicillin-resistant Staphylococcus aureus strain ATCC 700699 and moderate activity against S. aureus strain ATCC 29213