Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review.

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC50 values) of the isolated compounds that could be a guide for drug development.

Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: a review of recent articles.

BACKGROUND: Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis. MAIN TEXT: We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020. Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries. CONCLUSIONS: It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.

Antioxidant and hepatoprotective potentials of active fractions of Lannea barteri Oliv. (Anarcadiaceae) in rats.

INTRODUCTION: Lannea barteri is used in the folkloric treatment of many disease states ranging from epilepsy, diarrhoea, oedema and ulcers, etc. This study investigated the antioxidant and hepatoprotective potentials of methanol (MFLB), n-hexane (nHFLB) and ethyl acetate (EFLB) leaf fractions of L. barteri and identified the active metabolites. MATERIALS AND METHODS: The in vitro models used were 1, 1-diphenyl-1-picrylhydrazyl (DPPH), reducing power and thiobarbituric acid assays while in the in vivo model, carbon tetrachloride-induced oxidative liver damage in albino rats was used, and the biomarkers assayed were aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), serum total protein, serum direct and total bilirubin. Also, histopathological examination of the liver, high performance liquid chromatography (HPLC) profiling and liquid chromatography-mass spectroscopy-electrospray ionization (LC-MS-ESI) analysis of the fractions were done. RESULTS: In the in vitro assays, the decreasing order of DPPH free radical scavenging activity of the ascorbic acid and fractions at 400 µg/ml is as follows: ascorbic acid (86.6%), MFLB (52.8%), EFLB (36.6%), and nHFLB (28.1%). The percentage scavenging activity of the samples at 400 µg/ml in the TBA followed this pattern: ascorbic acid (117.1%), MFLB (82.2%), nHFLB (80.0%), and EFLB (46.9%). The ascorbic acid elicited highest reducing power (42.6%), followed by MFLB (22.5%), nHFLB (13.7%), and EFLB (-0.93%). The in vivo study showed significant (p < 0.0001) reduction in serum AST, ALT, and direct bilirubin with a non-significant reduction in ALP, total bilirubin and MDA, and mild elevation in total protein. Histopathological studies revealed a restorative effect on liver architecture. The phytochemical analyses revealed the presence of resins, terpenoids, flavonoids, carbohydrates, alkaloids, reducing sugar, saponins, tannins and proteins. HPLC-ESI-MS analysis revealed the presence of potentially bioactive compounds in L. barteri fractions. CONCLUSION: The fractions from L. barteri leaf possessed in vitro antioxidant and hepatoprotective potentials against CCl4-hepatic oxidative damage; therefore, proper isolation and characterization of these identified bioactive compounds responsible for the observed effects are ongoing.

Evaluation of Methanol-Dichloromethane Extract of Stemonocoleus micranthus Harms (Fabaceae) Stem Bark for Anti-Inflammatory and Immunomodulatory Activities.

BACKGROUND: The stem bark decoction of Stemonocoleus micranthus Harms (Fabaceae) is most widely used traditionally as a remedy for various diseases such as malaria and boil. In this study, the anti-inflammatory and immunomodulatory activities of the methanol-dichloromethane extract (MDE) from the stem bark of the plant in rodents were evaluated. METHODS: The carrageenan-induced rat paw oedema, cotton pellet-induced granuloma in rat, and xylene-induced ear oedema in mice were used to study the anti-inflammatory activity of methanol-dichloromethane extract of Stemonocoleus micranthus (MDESm) (100, 200, and 400 mg/kg). The effects of MDESm (100, 200, and 400 mg/kg) on cyclophosphamide-induced immunosuppression, neutrophil adhesion, carbon clearance, and haematological and biochemical parameters were carried out to study its immunomodulatory activity in mice. RESULT: MDESm (100 mg/kg, p.o.) significantly (p < 0.05) inhibited carrageenan-induced oedema by 57.1% at 5th h posttreatment compared with control. At 100 mg/kg, p.o., MDESm significantly (p < 0.05) reduced cotton pellet-induced granuloma by 39.28% and nonsignificantly reduced xylene-induced ear oedema by 34.1%. Treatment with MDESm (100 and 400 mg/kg) nonsignificantly abolished the neutropenia caused by cyclophosphamide with a percentage neutrophil reduction of 0 and -14.86%, respectively, while MDESm (200 mg/kg) and levamisole (50 mg/kg) had a nonsignificant reduction in neutrophil count (10.16 and 31.40%), respectively, all compared to the distilled water-treated group with a neutrophil count of -9.82%. MDESm at doses of 100 and 200 mg/kg increased phagocytic index by 0.0447 ± 0.00762 and 0.0466 ± 0.00703, respectively, although not significantly when compared to the control group with a value of 0.0226 ± 0.02117. There was a decrease in WBC and lymphocyte counts in MDESm- (200 mg/kg) treated group, suggesting immunosuppressive potential at this dose. MDESm caused a dose-dependent decrease in ALT and core liver enzymes, suggesting a hepatoprotective effect. The acute toxicity test revealed that MDESm is safe in mice with an oral lethal dose (LD50) of >5 g/kg. CONCLUSION: The methanol-dichloromethane extract of Stemonocoleus micranthus Harms possesses mild anti-inflammatory and immunomodulatory activities which may be more pronounced upon fractionation and purification. Therefore, more investigations are needed to explore these activities further.

Antibiotics Development and the Potentials of Marine-Derived Compounds to Stem the Tide of Multidrug-Resistant Pathogenic Bacteria, Fungi, and Protozoa.

As the search for new antibiotics continues, the resistance to known antimicrobial compounds continues to increase. Many researchers around the world, in response to antibiotics resistance, have continued to search for new antimicrobial compounds in different ecological niches such as the marine environment. Marine habitats are one of the known and promising sources for bioactive compounds with antimicrobial potentials against currently drug-resistant strains of pathogenic microorganisms. For more than a decade, numerous antimicrobial compounds have been discovered from marine environments, with many more antimicrobials still being discovered every year. So far, only very few compounds are in preclinical and clinical trials. Research in marine natural products has resulted in the isolation and identification of numerous diverse and novel chemical compounds with potency against even drug-resistant pathogens. Some of these compounds, which mainly came from marine bacteria and fungi, have been classified into alkaloids, lactones, phenols, quinones, tannins, terpenes, glycosides, halogenated, polyketides, xanthones, macrocycles, peptides, and fatty acids. All these are geared towards discovering and isolating unique compounds with therapeutic potential, especially against multidrug-resistant pathogenic microorganisms. In this review, we tried to summarize published articles from 2015 to 2019 on antimicrobial compounds isolated from marine sources, including some of their chemical structures and tests performed against drug-resistant pathogens.

Nutrition, malnutrition, and leishmaniasis.

Leishmaniasis is a vector-borne infectious disease with a long history of infecting humans and other animals. It is a known emerging or resurging disease. The host nutritional state has an indispensable role in defense against pathogens. The host defense system disorganization as a result of undernutrition is responsible for asymptomatic infections and even severe diseases. Host susceptibility and pathophysiologic severity to infection can be aggravated owing to undernourishment in a number of pathways, and infection also may aggravate preexisting poor nutrition or further increase host susceptibility. This study suggests that there may be some relationship between malnutrition and the endemicity of the parasite. The susceptibility to and severity of leishmanial infection can be altered by the body weight and serum levels of micronutrients. Nutrition not only affects the vulnerability of the host but also may affect the desire of sandfly to bite a specific host. Apart from host defense mechanism, nutritional stress also greatly influences vector competence and host-seeking behavior, especially during larvae development. The host and sandfly vector nutritional states could also influence the evolution of the parasite. It is essential to elucidate the roles that diets and nutrition play in the leishmanial life cycle. The aim of this article is to review the influences of nutrition and diets on the host susceptibility and severity of infection, preemptive and therapeutic strategy feedback, parasite evolution, and vector competence.

Evaluation of physicochemical and antioxidant properties of two stingless bee honeys: a comparison with Apis mellifera honey from Nsukka, Nigeria.

OBJECTIVE: Several physical, biochemical and antioxidant properties of two Nigerian stingless bee honey varieties (Melipona sp. and Hypotrigona sp.) were compared with Apis mellifera honey using standard analytical procedures. RESULTS: The mean pH of Apis mellifera, Hypotrigona sp. and Melipona sp. honeys were 4.24 ± 0.28, 3.75 ± 0.11 and 4.21 ± 0.37 respectively. The mean moisture contents of the honeys were 11.74 ± 0.47, 17.50 ± 0.80, and 13.86 ± 1.06%. Honey samples from Hypotrigona sp. when compared with other honey samples had the highest mean total dissolved solids (370.01 ± 22.51 ppm), hydroxymethylfurfural (16.58 ± 0.37 mg/kg), total acidity (35.57 ± 0.42 meq/kg), protein content (16.58 ± 0.37 g/kg), phenol content (527.41 ± 3.60 mg/kg), and ascorbic acid (161.69 ± 6.70 mg/kg), antioxidant equivalent-ascorbic acid assay value (342.33 ± 0.78 mg/kg) as well as ferric reducing power (666.88 ± 1.73 µM Fe(II)/100 g) (p < 0.05). Several strong correlations were observed among some of the parameters of the honeys. This is the first study to compare the properties of Nigerian honey bees. Our results suggested that these honeys (specifically Hypotrigona sp. honey) is a good source of antioxidants comparable to A. mellifera honey.