Unveiling Antimicrobial Potential of Novel Pyrrolo[2,3‐ <i>d</i> ]pyrimidine Linked 1,3,4‐Oxadiazole–1,2,3‐Triazole Conjugates Through Synthesis, In Vitro, and In Silico Studies

ABSTRACT To produce novel antimicrobial drugs, a series of pyrrolo[2,3‐ d ]pyrimidine‐linked dual heterocyclic hybrids were developed, synthesized, and characterized extensively with infrared, 1 H/ 13 C‐nuclear magnetic resonance, and mass spectra along with elemental analysis. The synthesized scaffolds were tested in vitro for their antibacterial and antifungal properties as proof of the notion of creating new antimicrobial medicines with novel pharmacophore moieties. A preliminary examination of the antibacterial activity of the produced compounds against all sensitive microbes demonstrated the potency of compounds 6a, 6c, 6e, 6i, and 6j . Compared to itraconazole, compounds 6e and 6i showed antifungal efficacy against Candida albicans with MICs of 6.25 and 25 µg mL ‒1 . All the produced analogs were initially examined in silico against the targeted protein, CYP51, which indicated analogs 6a, 6c, 6e , and 6j , as well as several other compounds, as potential inhibitors. Docking studies indicate that H‐bonding residues Tyr 132 (A) (2.91 Å), Arg 381 (A) (2.90 Å), Gly 472 (A) (2.86 Å), and His 468 (A) (3.02 Å) bind strongly to C. albicans sterol 14 α ‐demethylase receptor (PDB: 5TZ1). These bioactive compounds have good pharmacokinetics and bioavailability because they are nontoxic, have strong ADME properties, and comply with the main drug rules, such as Lipinski and Veber. This study found that combining the pyrrolo[2,3‐ d ]pyrimidine scaffold with 1,3,4‐oxadiazole via a 1,2,3‐triazole linker is a successful method for developing antibacterial and antifungal medicines.