Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

Abstract

Antimicrobial resistance was one of the top priorities for global public health before the start of the 2019 coronavirus pandemic (COVID-19). Moreover, in this changing medical landscape due to COVID-19, finding new organic structures with antimicrobial and antiviral properties is a priority in current research. The Biginelli synthesis that mediates the production of pyrimidine compounds has been intensively studied in recent decades, especially due to the therapeutic properties of the resulting compounds, such as calcium channel blockers, anticancer, antiviral, antimicrobial, anti-inflammatory or antioxidant compounds. In this review we aim to review the Biginelli syntheses reported recently in the literature that mediates the synthesis of antimicrobial compounds, the spectrum of their medicinal properties, and the structure–activity relationship in the studied compounds.

Pyridine Compounds with Antimicrobial and Antiviral Activities

“…The antibacterial activity data indicate that the analogs with halogen and nitro substituents emerged as promising antimicrobials, showing better to moderate activity, while analogs bearing chloro and methoxy substituent showed better antifungal activities, see bold compounds ( Table 7 ). Saleh et al [ 62 ] synthesized pyridine-fluorophenyl[ 1 , 3 , 5 ]triazines 148a – 148b starting from 2,4,6-trichloro -1,3,5-triazine 144 , and pyridin-3-amines 145 , via intermediates 146 and 147 , and by using in the last step a Suzuki coupling reaction ( Scheme 32 ). Compounds 148a and 148b showed excellent antibacterial activity against S. epidermidis , with MIC values of 16 μg mL −1 and 32 μg mL −1 , respectively, taking Streptomycin sulfate as standard (MIC > 16 μg mL −1 ).…”

“…Both compounds 202a – 202b exhibited better activity on Staphylococcus aureus when compared to standard, Gentamycine. Devineni et al [ 85 ] synthesized compounds 205a – 205d by reaction of 2-amino-2,3-dihydro-1 H -2λ 5 -[ 1 , 3 , 2 ]diazaphospholo[4,5-b]pyridin-2-one 203 and compounds 204 ( Scheme 45 ). Urea derivatives 205a , 205b , 205c , and 205d showed growth of inhibition against all the tested bacterial strains B. cereus ATCC 11778, S. faecalis MTCC 0459, E. coli ATCC 9637, and P. marginalis MTCC-2758.…”

“…Ramsay (1877) synthesizes pyridine for the first time, by the reaction of acetylene with hydrogen cyanide in a red-hot iron tube furnace, this being the first synthesized heterocycle [ 1 ]. Arthur Hantzsch later synthesized (1881) pyridine compounds by the synthesis that bears his name, through a multicomponent reaction, starting from a β-ketoester, an aldehyde and ammonia [ 2 , 3 ]. An important role of pyridine is that it is used as an organic solvent or as ligand for coordination complexes [ 4 , 5 , 6 , 7 , 8 ].…”

“…The recent literature mentions various series of compounds containing the pyridine nucleus, as a unique heterocycle, and with other heterocycles or fused with other heterocycles, which have remarkable antibacterial, antifungal and antiviral properties [ 1 , 9 , 10 , 11 , 12 , 13 ]. The presence of an additional heterocycle compared to the pyridine one in the bioactive molecule proved to be beneficial in the sense that it intensified the therapeutic properties of the antimicrobial and antiviral ones, and also widened their range [ 3 , 4 , 5 , 6 , 7 , 8 ]. Moreover, the presence of certain organic groups, such as amino, hydroxy, methoxy, sulfamide, hydrazide, etc., increase the biological activities of the compounds, as noted in the literature.…”

In Melting Points We Trust: A Review on the Misguiding Characterization of Multicomponent Reactions Adducts and Intermediates

“…Development in MCRs is notorious, especially over the last two decades [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Today we have, via these multicomponent transformations, rapid and one-pot access to diverse and complex libraries of bioactive compounds and to synthetic molecules with technological potentials [ 21 ].…”