Repurposing of Benzimidazole Scaffolds for HER2 Positive Breast Cancer Therapy: An In-Silico Approach.

BACKGROUND: A newer trend has been seen recently to reuse the conventional drugs with distinct indications for the newer applications to speed up the drug discovery and development based on earlier records and safety data. Most of the non-cancerous agents could afford a little or tolerable side effects in individuals. However, the repositioning of these non-cancerous agents for successful anticancer therapy is an outstanding strategy for future anti-cancer drug development. Since more diverse and selective cancer drug targets are being discovered and developed, the approved drug collections are particularly useful to quickly identify clinically advanced anticancer drugs against those targets. OBJECTIVE: Antihelminthic drugs such as Mebendazole and Albendazole (Benzimidazole class) have been reported to exhibit cytotoxicity (or anticancer activities) against several types of cancer. Therefore, this study aims to repurpose the benzimidazole scaffold for breast cancer treatment. METHODS: In the present study, three hydrazone analogs having a benzimidazole motif in their structural frame were synthesized. Their in-silico binding studies against HER2 receptor (PDB ID: 4LQM) and ADMET studies were carried out using Accelrys drug discovery studio 4.1. Cytotoxicity of the synthesized compounds against HER2 overexpressed MCF-7 cell lines was determined by MTT assay. RESULTS: One of the compounds 2-[2-(2,4-dinitrophenyl)hydrazinylidene]-2,3-dihydro-1H-benzimidazole (U1) has shown good cytotoxicity when compared to the standard Lapatinib, which is a well known HER2 inhibitor. CONCLUSIONS: Thus, the designed benzimidazole scaffold might serve as the best leads for treating breast cancer, which is additionally confirmed by performing their docking study via Accelrys discovery studio.

Pharmacological Uses of the Plants Belonging to the Genus Commiphora.

Natural products have a unique place in the healthcare industry. The genus Commiphora emerged as a potential medicinal source with huge benefits as evidenced through its use in various traditional and modern systems of medicine. Therefore, we aimed to prepare a concise review on the pharmacological activities and the indigenous uses of various plant species belonging to the genus Commiphora along with the structural information of various active botanical ingredients present in these plants based on the published literatures and scientific reports. To collect the published literatures on Commiphora in various journals; to study and classify the available information on the pharmacological uses and chemical constituents; and to present the gathered information as a precise review to serve as a potential reference for future research. Pharmacological and phytochemical data on Commiphora plant species were collected from various journals, books, reference materials, websites including scientific databases, etc. for compilation. This review article describes the various pharmacological properties of plants of Commiphora species viz., anti-arthritic and anti-inflammatory, anti-atherogenic, antibacterial, anti-coagulant, antidicrocoeliasis, anti-epileptic, anti-fascioliasis, anti-fungal, anti-heterophyidiasis, anti-hypercholesterolemic, anti-hyperlipidemic, anti-hypothyroidism, anti-obesity, anti-osteoarthritic, antiosteoclastogenesis, anti-oxidant, anti-parasitic, anti-pyretic, anti-schistosomiasis, anti-septic, antithrombotic, anti-ulcer, cardioprotective, COX enzyme inhibitory, cytotoxic /anti-carcinogenic/anticancer, DNA cleavage, hypotensive, inhibits lipid peroxidation, inhibits NO and NO synthase production, insecticidal, local anesthetic, molluscicidal, smooth muscle relaxant, and tick repellent activities along with toxicity studies. Furthermore, the review also included various secondary metabolites isolated from various species of Commiphora genus along with their chemical structures serving as a ready resource for researchers. We conclude that the plant species belonging to the genus Commiphora possesses abundant pharmacological properties with a huge treasure of diverse secondary metabolites within themselves. This review indicates the necessity of further in-depth research, pre-clinical, and clinical studies with Commiphora genus, which may help to detect the unidentified potential of the Commiphora plant species.