naphthoquinones and Schistosomiasis

Schistosomiasis is the second most prevalent parasitic infectious disease after malaria, which affects millions of people worldwide and causes health and socioeconomic problems. The snail Biomphalaria glabrata is an intermediate host for the helminth, which is the causative agent of schistosomiasis: Schistosoma mansoni. One crucial strategy for controlling the disease is the eradication of the snail host. Niclosamide is the unique molluskicide applied in large-scale control programs, but its selectivity to other species is not adequate. Therefore, there is an urgent need to develop new molluskicides that are inexpensive, safe, and selective. Quinones are ubiquitous, playing important biological roles in fungi, plants, and others. Many synthetic molecules with relevant biological activities that contain the quinone nucleus in their structure are on the market in the therapy of cancer, malaria, or toxoplasmosis, for example. Derivatives of quinones are tools in the development of new molluskicides for Abbott laboratories. In the present work, 3-aryl-2‑hydroxy-1,4-naphthoquinones (ANs) were tested for molluskicide activity against Biomphalaria glabrata. The lethal concentration was determined for 48 h of continuous exposure. The naphthoquinones were found to have molluskicide properties. AN-15 was recorded as the highest mortality. Additionally, this analog exhibited in silico reduced ambient toxicity when compared to niclosamide. The findings of this study demonstrate that 3-aryl-2‑hydroxy-1,4-naphthoquinones are effective for the management of Biomphalaria glabrata under laboratory conditions.

Topics: Animals; Biomphalaria; Humans; Naphthoquinones; Niclosamide; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni

Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-β and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.

Topics: Animals; Anthelmintics; Anti-Inflammatory Agents; Antioxidants; Catalase; Female; Granuloma; Immunoglobulin G; Interleukin-10; Interleukin-13; Interleukin-17; Interleukin-4; Liver; Male; Mice; Naphthoquinones; Praziquantel; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Schistosomicides; Sulfhydryl Compounds; Superoxide Dismutase; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

The rising costs of chemotherapy and synthetic molluscides have led to an increasing interest in plants which are lethal to the intermediate host of schistosomiasis (bilharzia). Over one thousand species have been tested but only a few have been phytochemically examined. Approximately fifty molluscicidal compounds have so far been isolated from plants, including saponins, terpenoids, flavonoids, naphthoquinones and tannins. The saponins from Phytolacca dodecandra are the most active and have been successfully employed in field tests. The latest results in this area and the problems involved in the use of plants and natural products for the control of schistosomiasis are discussed here.

Topics: Animals; Humans; Naphthoquinones; Plants, Medicinal; Saponins; Schistosomiasis; Schistosomicides; Sesquiterpenes; Species Specificity; Tannins

Skin penetration by Schistosoma mansoni cercariae may be blocked by 1,4-and 1,2-naphthoquinones applied topically. Of 23 naphthoquinone derivatives synthesized, 15 afforded almost complete protection when applied in solution to the tails of mice 24 hours before exposure to cercariae. On the basis of present evidence the 5-carbon atom side chain present in naturally occurring lapachol seems to be important for activity, and this is in accord with the previous observation that effective protective agents are liposoluble. Topically applied cercarial penetration inhibitors are presently the only prophylactic agents available for use in the field.

Topics: Administration, Topical; Naphthoquinones; Schistosoma mansoni; Schistosomiasis

Topics: Acrylic Resins; Administration, Topical; Animals; Anthelmintics; Ethers, Cyclic; Mice; Naphthoquinones; Ointments; Parasite Egg Count; Plant Extracts; Schistosoma mansoni; Schistosomiasis; Terpenes