New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis

Abstract

Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 μM and 83.3% at the concentration of 50 μM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs.

In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum

“…Along with molecular target-specific agents, some inhibitors targeting schistosomal enzymes have been reported to exhibit significant schistosomicidal effects [17, 18]. Additionally, other natural, chemotherapeutic compounds with antischistosomal activities and uncertain mechanisms of action have been identified [19, 20]. However, considering the high failure rate of these candidate compounds during pre-clinical and clinical trials, the development of alternative drugs requires further significant investment of time and resources.…”

Molecular docking, chemo-informatic properties, alpha-amylase, and lipase inhibition studies of benzodioxol derivatives

“…The 1,3-benzodioxol core structure present in the safrole compound, could be isolated from Crocus sativus L. and Ocotea pretiosa Mez plants, and interesting biological activities. The benzodioxole nucleus has been utilized in drug discovery for the synthesis of novel molecules with various biological activities, including anti-schistosomicidal, antiepileptic, analgesic, antituberculosis, and antimicrobial potentials [ 12 – 18 ]. On the other side, many structures containing carboxylic acid (COOH) group such as Nateglinide and tolrestat (Fig.…”

4‐Aminoquinolines Bearing a 1,3‐Benzodioxole Moiety: Synthesis and Biological Evaluation as Potential Antifungal Agents

“…The representative bioactive molecules containing this fragment are piperine, sanguinarine, chelerythrine, podophyllotoxin, steganacin, combretastatin A‐2, and so on ( Figure 1). They possess antioxidative, antibacterial, antifungal, antitumor and other biological activities [23–28] . In particular, the good bioavailability and low mammalian toxicity is of great interest [22,29] …”