Editorial on the research topic Beyond Borders: Exploring Diverse Roles of Heterocyclic Compounds in Combatting Infections and Cancer

Afzal Basha Shaik ^1,2* Richie Bhandare ^3,4 Mukhlesur Rahman ⁵ Kamal Dua ^6,7

• ¹ Vignan's Foundation for Science, Technology and Research, Guntur, Andhra Pradesh, India
• ² Center for Global Health Research, Saveetha Medical College & Hospital, Chennai, Tamil Nadu, India
• ³ College of Pharmacy, Ajman University of Science and Technology, Ajman, United Arab Emirates
• ⁴ Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, Ajman, United Arab Emirates
• ⁵ University of East London, London, United Kingdom
• ⁶ Australian Research Centre in Complementary and Integrative Medicine, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia
• ⁷ Department of Pharmacy, Graduate School of Health, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia

resistance, and even pan-drug resistance phenotypes, are collectively referred to by the acronym ESCAPE, encompassing Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae (De Oliveira DM et al, 2023). Recent developments in this area have shown the potential of heterocyclic compounds to offer more targeted and effective treatments with fewer side effects.Therefore, this Research Topic invited papers that showcased recent progress in medicinal and natural product chemistry, including the isolation & characterization, design, synthesis, and application of heterocyclic compounds as promising anti-infective and anticancer agents.This Research Topic covers a total of fourteen original research articles investigating ligands spanning broad therapeutic areas like breast/prostate cancer, inflammatory bowel disease, antitubercular ligands, antimicrobials, anticholinergic and antidiabetic. Seven papers focused on exploring heterocyclic compounds from natural products using various techniques such as molecular dynamics, nanoparticles, in-silico and GC-MS profiling and quantum analysis while the remaining papers emphasised the use of heterocyclic fragments for various therapeutics activities. derivatives of thymol and evaluating their antimicrobial properties. The synthesized compounds showed broad spectrum in-vitro antibacterial activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Among the derivatives, they identified a promising compound with the most potent antibacterial activity against both P. aeruginosa and MRSA. Furthermore, the most potent compound exhibited synergistic effects when combined with vancomycin, enhancing its antibacterial efficacy. In silico analysis of its physicochemical properties confirmed compliance with all drug-likeness criteria. Lastly, molecular docking studies revealed that the promising compound had a stronger binding affinity to the target protein than thymol, providing valuable insights into its potential mechanism of action. Additionally, their inhibitory potential against the InhA enzyme was assessed. Several molecules demonstrated significant activity against M. tuberculosis. Molecular docking analysis revealed key interactions between these compounds and the target enzyme, while molecular dynamics (MD) simulations confirmed the stability of the quinoline-triazole conjugate complexes with InhA. Furthermore, the most potent compound underwent in silico ADME analysis to predict its pharmacokinetic properties. This study provides valuable insights into the development of novel, safe, and effective small-molecule therapeutics for tuberculosis treatment.Arif et al. reported the development of a novel isatin derivative capable of degrading estrogen receptor alpha (ERα) in estrogen-dependent breast cancer cells. A series of hydrazide derivatives were synthesized and evaluated in vitro for their antiproliferative activity against the MCF-7 (ER+) cell line. The effect of the most potent compound on ERα expression was further analyzed using Western blot analysis. Additionally, in silico pharmacokinetic predictions were conducted using various computational tools, including pkCSM, to assess the activity profiles of the synthesized compounds.Zhao et al. identified novel chrysin derivatives with promising therapeutic potential for inflammatory bowel disease (IBD). Among them, a potent compound exhibited significant inhibitory activity against TNF-α-induced monocyte adhesion to the colonic epithelium.Mechanistic studies revealed that this compound suppresses reactive oxygen species (ROS) production and downregulates the expression of ICAM-1 and MCP-1, key mediators of monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments further demonstrated its efficacy in mitigating colitis in animal models. These findings highlight the compound's potential as a promising candidate for IBD management.In summary, the fourteen original articles featured in this Research Topic have presented recent advancements in the application of heterocyclic scaffolds across various therapeutic areas, including breast cancer, inflammatory bowel disease, and tuberculosis. The collective findings of these studies offer valuable insights for researchers in organic and medicinal chemistry, particularly those focused on chemotherapy. This topic has also emphasized the challenge of antimicrobial resistance and underscores the significance of heterocycles as privileged structures in drug design, making it highly relevant to Frontiers readers in this field. The heterocyclic ring systems discussed herein may be of particular interest to medicinal chemists for the synthesis of bioactive compounds and the development of novel analogues, thereby contributing to chemotherapy drug discovery efforts and addressing the global issue of resistance.