The reaction of thiophene-2-carbohydrazide
1 or 5-bromothiophene-2-carbohydrazide
2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3
H-1,2,4-triazole-3-thione
5a-
e. The triazole derivatives
5a and
5b were reacted with different
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The reaction of thiophene-2-carbohydrazide
1 or 5-bromothiophene-2-carbohydrazide
2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3
H-1,2,4-triazole-3-thione
5a-
e. The triazole derivatives
5a and
5b were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3
H-1,2,4-triazole-3-thiones
6a–
e,
7a–
e,
8,
9,
10a and
10b in good yields. The in vitro antimicrobial activity of compounds
5a–
e,
6a–
e,
7a–
d,
8,
9,
10a and
10b was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds
5a,
5b,
5e,
5f,
6a–
e,
7a–
d,
8,
9,
10a and
10b showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria
Escherichia coli, and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds
5e,
6a–
e,
7a–
d and
10a exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC
50 < 25 μM). A detailed structural insight study based on the single crystals of compounds
5a,
5b,
6a,
6d and
10a is also reported. Molecular docking studies of the highly active antibacterial compounds
5e,
6b,
6d,
7a and
7d showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds
6d,
6e and
7d may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2).
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