## 1 Introduction  
In recent years, our research interest has focused on synthesizing new benzimidazole derivatives as potential anthelmintic agents against _Trichinella spiralis (T.spiralis)_, which causes trichinellosis [1, 2, 3]. This is supported by the fact that the current drugs used to treat this zoonotic disease--the benzimidazole anthelmintics albendazole and mebendazole--are highly effective in the initial phase of infection. They expel infective intestinal larvae and adult worms from the small intestinal epithelium of the host, inhibit females from producing newborn larvae, and kill larvae during the migration stage [4]. However, they are only moderately effective against encapsulated larvae in muscle tissue. These drugs also have poor bioavailability and numerous adverse effects, including headaches, nausea,vomiting, fever, and elevated liver enzymes. Patients with pre-existing liver damage or dysfunction are especially vulnerable to more severe side effects, including leukopenia, anemia, thrombocytopenia, and pancytopenia [5]. In addition, there is increasing evidence of emerging resistance to benzimidazole anthelmintics [6; 7]. The most severe complications of Trichinella infection, however, are associated with involvement of the central nervous system (CNS) [8]. The presence of _Trichinella_ larvae in the CNS causes damage to blood capillaries such as vasculitis and perivascularitis, which are responsible for diffuse or focal lesions, in addition to granulomatous and allergic inflammatory reactions [9]. In this context, neurotrophicillosis is among the most serious complications of severe trichinellosis, along with myocarditis and thromboembolic events, and is often associated with fatal outcomes. Treatment of neurotrophicillosis requires the use of antiparasitic drugs that can cross the blood-brain barrier. Unfortunately, alendazole and mebendazole do not meet this requirement. Therefore, there is a need for novel and safe anti-_Trichinella_ drugs, especially with efficacy against parasites localized in the CNS. Our previous studies have shown that simple structural modifications of the key benzimidazole scaffold, especially the addition of another heterocyclic, such as 1,3,5-triazine [3], thiophene [3], 1,3-benzodioxole [1; 3; 10], indole [3], etc., is a successful design strategy for new hybrid molecules with synergistic activity against _T. spiralis_. Among the newly synthesized compounds with the highest larvicidal efficacy (58.41% at 50 \(\upmu\)g/mL concentration after 24 h incubation), the fused triazinobenzimidazole with thiophen-2-yl moiety stands out [3]. On the other hand, the thiophene ring is a key structural motif in numerous antiparasitic compounds, demonstrating potent activity against parasites, including _Leishmania_[11; 12; 13], _Plasmodium_[14; 15], and _Trypanosoma_ spp. [16; 17]. In addition, numerous literary sources confirm the importance of the thiophene scaffold as a potential agent for the central nervous system [18; 19]. In light of recent findings, the synthesis of hybrid molecules combining both benzimidazole and thiophene pharmacophores is emerging as a promising strategy for finding new antiparasitic agents to treat neurotrichinellosis. In the present study, we describe the synthesis of two groups of benzimidazole derivatives containing a thiophene or other heteroaromatic fragment: methanamines and hydrazones. We then discuss how small structural differences affect the activity of these compounds on the isolated muscle larvae of the parasite _T. spiralis_. In addition to testing the anthelmintic activity of the benzimidazoles, we also predicted their physicochemical properties and drug-likeness using an in silico approach to further explore the polypharmacology of these benzimidazole derivatives. The next phase of this study involved carrying out tubulin polymerization inhibition assays to clarify the possible antiparasitic action mechanism.