Infectious diseases caused by microorganisms (bacteria, fungi, bacillus, etc.) have increased dramatically in recent years and represent a serious threat to public health all around the world, killing thousands of people worldwide per year. In spite of many significant advances in antimicrobial therapy, the widespread use and misuse of antimicrobials (antibiotics, antifungals, antituberculosis, etc.) have caused the emergence of microbial resistance to drugs, and led to an increase in difficult-to-eradicate infections. In particular, the emergence of drug and multidrug resistant bacteria (gram-positive and gram-negative) and fungi have reached on alarming level in many countries around the world and become a serious problem in the treatment of microbial diseases and a major threatening for public health. As a matter of fact, World Health Organization has been introduced antimicrobial resistance as one of ten’s threats to global health in 2019. The most common multidrug resistant bacteria are the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) and from fungi Candida albicans, rise up the most serious problems. Resistance to drugs is acquired through several mechanisms that include the over expression of antibiotic-inactivating enzymes (e.g. extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae), increased activity of efflux pumps, and mutations of the outer membrane or, target enzymes. On the other hand, the antibacterial and antifungal mechanism of actions are known for some drugs (e.g. kinase inhibitors, DNA-gyrase inhibitors) and are unknown or uncertain for others. This is why it is compulsory to bring new insides related to resistance mechanism and mechanism of actions of antimicrobials.

Over the past few decades, there has been a decline in antimicrobial drug development, resulting in fewer new antimicrobial drug approvals. Antimicrobial drug development has not kept pace with evolving microbial resistance to the existing therapeutic armamentarium of antimicrobial drugs, thus limiting treatment options for patients. Rising incidences of infectious diseases awareness amongst the healthcare professionals and the patients and commercialization of pipeline products are boosting the market growth. Also, growing resistance of infection to the drug therapies, high price of drugs, competition between generic manufacturers and perilous reimbursement policies are impede market growth. Therefore, to overcome all these disadvantages mentioned above, there is thus an urgent need to develop new efficient and well-tolerated antibacterial and antifungal compounds.

During the last 50 years, six and five member ring azaheterocycles, especially (di-)-azine (pyridine, quinoline, pyridazine, phthalazine), (di- and tri-)-azoles (imidazole, benzimidazole, triazole), and their derivatives, emerging as crucial privileged scaffolds in modern medicinal chemistry and drug discovery, a large variety of biological activities being described for these compounds, these including antibacterial and antifungal one. Practically more than 90% of the existing market drugs contain in their molecule a 5- or 6- member ring azaheterocycle. In many cases, the synthesis of these five and six member ring azaheterocycles derivatives still remain a challenge for scientific communities, because the conventional thermal heating (TH) synthesis is often inefficient, with variable yields, the formation of by-products, expensive and harsh reaction conditions (high temperature, long reaction time, great amounts of solvents, catalysts, etc.

All these drawbacks of conventional TH synthesis cause serious problems from economic, social and environmental point of view. In order to overcome all these problems of conventional TH synthesis, over the last few decades, microwave (MW) and ultrasound (US) irradiation has become an alternative modern and successful tool applied in organic and medicinal chemistry. Comparative with conventional TH, the use of MW and US in chemical reactions has some crucial advantages such us: higher yields and better product purities, the possibility to reach new selectivity and new reactivity, reduced reaction times, etc.. In addition, having milder reaction conditions, less or suppressed side reactions, energy saving, using small or no amounts of solvents, the reactions fulfill more than half of the twelve principles of “Green Chemistry”, and become environmentally friendly.

Taking into considerations all the above mentioned data, the critical societal demands, as well as the stringent request from pharmaceutical industry and medical sector for new antimicrobial drugs, it appear as a necessity to find new six and five member ring azaheterocycles with antimicrobial and antifungal activity and to elaborate new eco-friendly methods for synthesis.