In vitro and in silico Approaches to the Identification of New Compounds
with Antibacterial Profile
Carlos R. Rodrigues, Bruno Leal, Kely N. De Oliveira, Ariane S. S. R. Ferreira, Alice Bernardino, Ricardo J. Nunes, Vitor Ferreira, Maria C. De Souza, Anna C. Cunha, Helena C. Castro
The emergence of multidrug-resistant bacterial strains is a
world problem that increases the need for new and more
effective antimicrobials. On that purpose, derivatives of cyclic
systems may serve as new leads for discovering new active
molecules. In this work we evaluated the antibacterial profile of
243 molecules derived from the systems thienopyridine,
pyrazolopiridine, quinolone, chalcone, hydrazone and lapachone
against Gram-positive and Gram-negative susceptible and
multiresistant strains also comparing them with antibiotics of
clinical use. Our results showed that among the 243 molecules
tested, only eight derivatives were active with promissing MIC
values (2-64mg/mL). Our theoretical in silico analysis showed
that all active compounds fulfilled Lipinski rule of five
(molecular weight = 344.37–409.24, clogP = 3.15–4.11, nHBA
= 6–7, and nHBD = 2), similarly to commercial drugs as well as
presented better druglikeness values (from -3.68 to 0.12) than
chloramphenicol (-4.61) and linezolid (-4.08). Most of the
active derivatives presented a low in silico toxicity risk profile,
similar to oxacillin, ampicillin, and penicillin G, and even lower
than that observed for chloramphenicol and linezolid.
Theoretically HOMO and the electrostatic protential distribution
may be contributing for this safer profile. This study used
computacional tools and may help to deal with an important
world health problem. Full Text
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