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Antimicrobial and anticancer activity of some novel fluorinated thiourea derivatives carrying sulfonamide moieties: synthesis, biological evaluation and molecular docking

View Article: PubMed Central

ABSTRACT

Background: Various thiourea derivatives have been used as starting materials for compounds with better biological activities. Molecular modeling tools are used to explore their mechanism of action.

4a4c4d4a: A new series of thioureas were synthesized. Fluorinated pyridine derivative showed the highest antimicrobial activity (with MIC values ranged from 1.95 to 15.63 µg/mL). Interestingly, thiadiazole derivative and coumarin derivative exhibited selective antibacterial activities against Gram positive bacteria. Fluorinated pyridine derivative was the most active against HepG2 with IC50 value of 4.8 μg/mL. Molecular docking was performed on the active site of MK-2 with good results.

4a: Novel compounds were obtained with good anticancer and antibacterial activity especially fluorinated pyridine derivative and molecular docking study suggest good activity as mitogen activated protein kinase-2 inhibitor.

No MeSH data available.


Co-crystallized ligand in the active site of mitogen activated kinase (MK-2)
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Fig5: Co-crystallized ligand in the active site of mitogen activated kinase (MK-2)

Mentions: One of the most important enzymes that controls signal transduction and cell proliferation is mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2 or MK-2) [39]. Discovering new inhibitors for this key enzyme has received attention as a strategy in the seek for novel anticancer agents [40]. Among the newly discovered inhibitors for this enzyme, several urea and thiourea derivatives have showed good activity [41]. In the present research, several thiourea derivatives were synthesized and evaluated for their cytotoxic activity. The most active derivatives 3c and 4a–4c were docked on the active site of MK-2 enzyme in a trial to suggest a mechanism of action for their cytotoxic activity. The protein data bank file (PDB: 3WI6). The file contains MK-2 enzyme co-crystalized with an inhibitor. All docking procedures were achieved by MOE (Molecular Operating Environment) software 10.2008 provided by chemical computing group, Canada. The inhibitor interacts with MK-2 active site with four hydrogen bonds involving Glu 190, Leu 141, Asn 191 ans Asp 207 (Fig. 5). The docking protocol was validated by redocking of the ligand on the active site of MK-2 enzyme with energy score (S) = −15.4978 kcal/mol and root mean square deviation (RMSD) = 1.1457.Fig. 5


Antimicrobial and anticancer activity of some novel fluorinated thiourea derivatives carrying sulfonamide moieties: synthesis, biological evaluation and molecular docking
Co-crystallized ligand in the active site of mitogen activated kinase (MK-2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5383913&req=5

Fig5: Co-crystallized ligand in the active site of mitogen activated kinase (MK-2)
Mentions: One of the most important enzymes that controls signal transduction and cell proliferation is mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2 or MK-2) [39]. Discovering new inhibitors for this key enzyme has received attention as a strategy in the seek for novel anticancer agents [40]. Among the newly discovered inhibitors for this enzyme, several urea and thiourea derivatives have showed good activity [41]. In the present research, several thiourea derivatives were synthesized and evaluated for their cytotoxic activity. The most active derivatives 3c and 4a–4c were docked on the active site of MK-2 enzyme in a trial to suggest a mechanism of action for their cytotoxic activity. The protein data bank file (PDB: 3WI6). The file contains MK-2 enzyme co-crystalized with an inhibitor. All docking procedures were achieved by MOE (Molecular Operating Environment) software 10.2008 provided by chemical computing group, Canada. The inhibitor interacts with MK-2 active site with four hydrogen bonds involving Glu 190, Leu 141, Asn 191 ans Asp 207 (Fig. 5). The docking protocol was validated by redocking of the ligand on the active site of MK-2 enzyme with energy score (S) = −15.4978 kcal/mol and root mean square deviation (RMSD) = 1.1457.Fig. 5

View Article: PubMed Central

ABSTRACT

Background: Various thiourea derivatives have been used as starting materials for compounds with better biological activities. Molecular modeling tools are used to explore their mechanism of action.

4a4c4d4a: A new series of thioureas were synthesized. Fluorinated pyridine derivative showed the highest antimicrobial activity (with MIC values ranged from 1.95 to 15.63 µg/mL). Interestingly, thiadiazole derivative and coumarin derivative exhibited selective antibacterial activities against Gram positive bacteria. Fluorinated pyridine derivative was the most active against HepG2 with IC50 value of 4.8 μg/mL. Molecular docking was performed on the active site of MK-2 with good results.

4a: Novel compounds were obtained with good anticancer and antibacterial activity especially fluorinated pyridine derivative and molecular docking study suggest good activity as mitogen activated protein kinase-2 inhibitor.

No MeSH data available.