Synthesis, Biological Profile, and Molecular Docking of Some New Bis- Imidazole Fused Templates and Investigation of their Cytotoxic Potential as Anti-tubercular and/or Anticancer Prototypes

Abstract

Background: There is a great need to discover more drugs with antimycobacterial activities to fight lung cancer and tuberculosis (two of the deadliest diseases world-wide). To our knowledge, the present study is the first to report antimycobacterial activity of imidazole-fused heterocycles. Objective: Construction of some bis-imidazole fused heterocycles with potential anti-tubercular and/or potent antitumor activities. Method: A series of bis-imidazole fused derivatives 6-8 and 13-16 was constructed using bis-phenacyl bromide derivative 2 as a synthetic platform. Compound 2 was also used to access bis-quinoxaline 20, bis-benzothiazine derivatives 23, and bisthiazolopyrimidine derivatives 26. The new bis-imidazole derivatives were evaluated for their anticancer activity against lung carcinoma cell line (A-549) using Cisplatin as a reference drug. The new compounds were also screened for their antitubercular activity against M. tuberculosis (ATCC 25177) using Isoniazid as a reference drug. Result: Among the new bis-imidazole derivatives, three examples showed remarkable antitumor activities while five other compounds showed high antimycobacterial activity. Conclusion: A novel series of bis-imidazole fused heterocycles was developed. Multiple prototypes of this new series showed remarkable anti-tubercular and/or potent antitumor activities.

Two Novel Regioisomeric Series of Bis-pyrazolines: Synthesis, In Silico Study, DFT Calculations, and Comparative Antibacterial Potency Profile against Drug-Resistant Bacteria; MSSA, MRSA, and VRSA

“…The biological profile of pyrazolines is dramatically correlated with the relative substitution pattern, especially at N-1, C-3, and C-5 positions. Similar to many other bis-heterocyclic compounds, − designing new classes of bis-3,5-diaryl pyrazolines has been attracting an increased attention over the last couple of decades due to their potential biological and pharmacological applications. − Like their parent heterocyclic pyrazolines, bis-3,5-diaryl pyrazoline derivatives, their bis-heterocyclic analogues, have been known for their high bioactive threshold. Many bioactive bis-3,5-diaryl pyrazolines were constructed from bis-1,3-diarylenone precursors. − …”

Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

“…[5] Among these products, the imidazole ring is considered one of the most important templates with a privileged structure in modern medicinal chemistry considering its comprehensive pharmacological spectrum and affinity for various bio targets. [6] Compounds containing imidazole ring have been reported as anticancer, [7,8] antibacterial, [9] antiviral [10] and antiepileptic. [11] The notable bioactivity of compounds carrying an imidazole ring is postulated to be because of its high polarity properties (experimental logP close to zero) due to the presence of two nitrogen atoms and the capability of imidazole ring to be a hydrogen bond donor allowing it to interact with molecular targets such as receptors and enzymes.…”

Novel Imidazole Liquid Crystals; Experimental and Computational Approaches

“…The imidazole ring is a well-known five-membered, nitrogen-containing heterocyclic scaffold. Interestingly, the imidazole-based molecules have emerged as a critical component of pharmaceutical and medical chemistry [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Imidazole derivatives have a wide range of industrial applications.…”