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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.


Fluorinated and thiourea anticancer agents
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Fig1: Fluorinated and thiourea anticancer agents

Mentions: Fluorinated compounds are intriguing for the development of pharmaceuticals, agrochemicals, and materials, and thus, much effort has been exerted to develop more general and efficient approaches for introducing fluorine atom(s) or fluoroalkyl group(s) into organic molecules [1–4]. The unique properties of fluoro organic molecules may arise from the properties such as (i) the greatest electronegativity of fluorine, (ii) the largest strength of the carbon–fluorine bond, (iii) the hardness and the low van der Waals interaction due to the low polarizability, (iv) the increased hydrophobicity, and (v) the second smallest atomic radius of the fluorine atom. These factors are operative singly or sometimes cooperatively to affect the pharmacological properties of the fluorinated molecules [5]. The majority of fluorinated drugs are constructed by five- and six-membered nitrogen heterocycles containing fluorine, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, and pentafluoroethyl groups [6]. An increasing number of fluorinated antimitotic/antitumour agents have now becoming available for cancer treatment. The most widely used are the 5-fluoropyrimidines such as 5-fluorouracil (5-FU) and 5-fluoro-2\-deoxyuridine (FdUrd) [7, 8], (Fig. 1). The thiourea derivatives represent one of the most promising classes of anticancer agents with a wide range of activities against various leukemia and solid tumors [9–17]. They play an important role as anticancer agents because of their good inhibitory activity against protein tyrosine kinases (PTKs), [10–13] human sirtuin type proteins 1 and 2 (SIRT1 and SIRT2), [14] topoisomerase II [15] and DNA repair synthesis [16]. Furthermore, fluorinated aryl thioureas represent a new class of potent anti-trypanosomal agents [18] and also a novel class of potent influenza virus neuraminidase inhibitors [19]. Thiocarlide is a pharmacologically important thiourea drug that is used as a therapeutic agent in the treatment of tuberculosis [20] and Phenethylthiazoylthiourea (PETT) derivatives (LY73497 and trovirdine HCl) [21, 22] have been discovered as potent inhibitors of HIV type 1, (Fig. 1).Fig. 1


Antimicrobial and anticancer activity of some novel fluorinated thiourea derivatives carrying sulfonamide moieties: synthesis, biological evaluation and molecular docking
Fluorinated and thiourea anticancer agents
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Fluorinated and thiourea anticancer agents
Mentions: Fluorinated compounds are intriguing for the development of pharmaceuticals, agrochemicals, and materials, and thus, much effort has been exerted to develop more general and efficient approaches for introducing fluorine atom(s) or fluoroalkyl group(s) into organic molecules [1–4]. The unique properties of fluoro organic molecules may arise from the properties such as (i) the greatest electronegativity of fluorine, (ii) the largest strength of the carbon–fluorine bond, (iii) the hardness and the low van der Waals interaction due to the low polarizability, (iv) the increased hydrophobicity, and (v) the second smallest atomic radius of the fluorine atom. These factors are operative singly or sometimes cooperatively to affect the pharmacological properties of the fluorinated molecules [5]. The majority of fluorinated drugs are constructed by five- and six-membered nitrogen heterocycles containing fluorine, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, and pentafluoroethyl groups [6]. An increasing number of fluorinated antimitotic/antitumour agents have now becoming available for cancer treatment. The most widely used are the 5-fluoropyrimidines such as 5-fluorouracil (5-FU) and 5-fluoro-2\-deoxyuridine (FdUrd) [7, 8], (Fig. 1). The thiourea derivatives represent one of the most promising classes of anticancer agents with a wide range of activities against various leukemia and solid tumors [9–17]. They play an important role as anticancer agents because of their good inhibitory activity against protein tyrosine kinases (PTKs), [10–13] human sirtuin type proteins 1 and 2 (SIRT1 and SIRT2), [14] topoisomerase II [15] and DNA repair synthesis [16]. Furthermore, fluorinated aryl thioureas represent a new class of potent anti-trypanosomal agents [18] and also a novel class of potent influenza virus neuraminidase inhibitors [19]. Thiocarlide is a pharmacologically important thiourea drug that is used as a therapeutic agent in the treatment of tuberculosis [20] and Phenethylthiazoylthiourea (PETT) derivatives (LY73497 and trovirdine HCl) [21, 22] have been discovered as potent inhibitors of HIV type 1, (Fig. 1).Fig. 1

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.