Triplex nucleic acid structures receive considerable attention due to their possible role in anti-gene therapy, several diseases as Friedreich's ataxia and Deoxyribonucleic acid (DNA) based nano-structures. The modulation of triplex formation and its stabilization using small molecules is one way to enhance their utility in such applications. Here, we synthesized five new Azacyanines (Azaethyl (2 b), Azapropyl (2 c), Azaisopropyl (2 d), Azabutyl (2 e), Azaisobutyl (2 f)) and assessed their affinity and selectivity towards polyd(A), polyd(T), polyd(A)⋅polyd(T) and polyd(A)⋅polyd(T)⋅polyd(T) along with the previously synthesized Azamethyl (2 a). Our UV-Vis, CD and competition dialysis results revealed that Azacyanines were selective towards polyd (A)⋅polyd(T)⋅polyd(T) triplex. They were stabilizing triplex structure to different degrees, the degree of stabilization being dependent on the alkyl chain length and branching on the benzimidazole ring. Thermal denaturation temperature of the triplex in the presence of Azacyanines was increasing in order: Azamethyl (2 a) > Azaethyl (2 b) > Azapropyl (2 c) > Azabutyl (2 e) > Azaisobutyl (2 f) > Azaisopropyl (2 d). Our results also demonstrate that, Azamethyl (2 a) was able to disproportionate polyd(A)⋅polyd(T) into intercalated polyd(A)⋅polyd(T)⋅polyd(T) complex.

Introduction: Topoisomerase II alpha (Topo IIα) has become one of the extensively exploited targets in chemotherapy due to its role in regulating the topological constraints of DNA during replication and transcription. Small molecules targeting Topo IIα’s activity such as etoposide (VP-16) and doxorubicin are extensively used in the treatment of many different types of cancer. Objective: Here, the effects of three small molecules, named as azacyanines, on Topo IIα have been assessed. Methods: In-vitro Topoisomerase IIα drug screening kit and agarose gel imaging were used for the assessment of Topo IIα’s activity. Results: Our results revealed that all the azacyanines investigated decreased the catalytic activity of Topo IIα dramatically. More importantly, the decrease in the catalytic activity of Topo IIα in the presence of azacyanines was higher than the presence of VP-16, which is a commercially available chemotherapy drug. Upon further investigation, it has been observed that Azamethyl’s catalytic inhibition of Topo IIα was concentration dependent and the catalytic activity of Topo IIα was almost completely abolished in the presence of 100.0 μM of Azamethyl. Conclusion: These findings reveal the potential of azacyanines as effective Topo IIα inhibitors and chemotherapeutic agents.

Purpose of review The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU). Recent findings Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors. Summary Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU.