Role of small molecules and nanoparticles in effective inhibition of microbial biofilms: A ray of hope in combating microbial resistance.

Microbial biofilms pose a severe threat to global health, as they are associated with deadly chronic infections and antibiotic resistance. To date, very few drugs are in clinical practice that specifically target microbial biofilms. Therefore, there is an urgent need for the development of novel therapeutic options targeting biofilm-related infections. In this review, we discuss nearly seventy-five different molecular scaffolds published over the last decade (2010-2023) which have exhibited their biofilm inhibition potential. For convenience, we have classified these into five different sub-groups based on their origin and design (excluding peptides as they are placed in between small molecules and biologics), namely, heterocycles; inorganic small molecules & metal complexes; small molecules decorated nanoparticles; small molecules derived from natural products (both plant and marine sources); and small molecules designed by in-silico approach. These antibiofilm agents are capable of disrupting microbial biofilms and can offer a promising avenue for future developments in human medicine. A hitherto review of this kind will lay a platform for the researchers to find new molecular entities to curb the serious menace of antimicrobial resistance especially caused by biofilms.

Conjugation as a Tool in Therapeutics: Role of Amino Acids/Peptides-Bioactive (Including Heterocycles) Hybrid Molecules in Treating Infectious Diseases.

Peptide-based drugs are gaining significant momentum in the modern drug discovery, which is witnessed by the approval of new drugs by the FDA in recent years. On the other hand, small molecules-based drugs are an integral part of drug development since the past several decades. Peptide-containing drugs are placed between small molecules and the biologics. Both the peptides as well as the small molecules (mainly heterocycles) pose several drawbacks as therapeutics despite their success in curing many diseases. This gap may be bridged by utilising the so called 'conjugation chemistry', in which both the partners are linked to one another through a stable chemical bond, and the resulting conjugates are found to possess attracting benefits, thus eliminating the stigma associated with the individual partners. Over the past decades, the field of molecular hybridisation has emerged to afford us new and efficient molecular architectures that have shown high promise in medicinal chemistry. Taking advantage of this and also considering our experience in this field, we present herein a review concerning the molecules obtained by the conjugation of peptides (amino acids) to small molecules (heterocycles as well as bioactive compounds). More than 125 examples of the conjugates citing nearly 100 references published during the period 2000 to 2022 having therapeutic applications in curing infectious diseases have been covered.