Ibrahim Chaaban

Synthesis and biological evaluation of new oxadiazoline-substituted naphthalenyl acetates as anticancer agents.

A series of new oxadiazoline-substituted naphthalenyl acetates 3a-e and oxadiazoline-substituted 4-methoxynaphthalenyl acetates 7b-e were synthesized and tested by the National Cancer Institute (NCI) for their in vitro anticancer activity. The two derivatives bearing acetoxy groups at the 1 and 3 positions of the phenyl ring 3c and 7c were the most active showing significant anticancer activity against all tested cancer cell lines, with GI50 values ranging from 0.175 to 3.91 μM, and 0.306-11.7 μM, respectively. The selectivity of compound 3c was greater for non-solid tumor cell lines. Computational prediction of molecular and pharmacokinetic properties revealed that both compounds are safe and compound 7c had a good drug-likeness score.

Synthesis and anti-proliferative activity of sulfanyltriazolylnaphthalenols and sulfanyltriazolylnaphthalene-1,4-diones

A series of new sulfanyltriazolylnaphthalenols (10a–f and 13a–f) and sulfanyltriazolylnaphthalene‐1,4‐diones (14a–f) were synthesized and evaluated against a panel of cancer cell lines. Among the tested compounds, 10b and 10d showed the best anti‐proliferative activity with GI50 values ranging from 2.72 to 10 and 3.13 to 13.1 µM, respectively, in several of the tumor cell lines tested. Compound 10d is highly selective toward leukemia cell lines and can be regarded as a good model for the development of new anti‐leukemic agents.

Synthesis and biological evaluation of novel benzoquinones as potential antimicrobial agents

New series of 2,5-dihydroxyphenyl-1,3-thiazoles 4a–l was synthesized by reacting 2,5-dihydroxyphenacyl bromide with various 4-aryl thiosemicarbazones 3a–l that on oxidation with ferric chloride yielded the corresponding N1-substituted benzylidene-N2-[3-aryl-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazines 5a–l. They were evaluated for antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria. They were also evaluated for their in vitro antifungal potential against Candida albicans. Almost all tested compounds were found to possess variable degrees of antimicrobial activity. The obtained data revealed that compounds 4b–h and 5e, 5f and 5l exhibited promising antimicrobial activity against the tested organisms of which compound 4b proved to be the most active.

Synthesis and evaluation of new phenolic derivatives as antimicrobial and antioxidant agents

New phenolic derivatives bearing hydrazine and 1,3,4-oxadiazole moieties were synthesized and evaluated for their in vitro antimicrobial and antioxidant activities. Most of the compounds revealed pronounced activity against Pseudomonas aeruginosa as well as promising antioxidant activities. N1-(2,5-Dihydroxybenzoyl)-N2-(4-methylphenylsulfonyl)hydrazine displayed promising activity against Escherichia coli and P. aeruginosa. N1-(2,5-Dihydroxybenzoyl)-N2-(2-naphthalenylmethylene)hydrazine was almost equipotent to the standard antioxidant vitamin C having scavenging activities of 84 and 93%, respectively. In vitro cytotoxicity study revealed that N1-(2,5-dihydroxybenzoyl)-N2-(2,3,4-trimethoxyphenylmethylene)hydrazine, N1-(2,5-dihydroxybenzoyl)-N2-(3,4,5-trimethoxyphenylmethylene)hydrazine, and N1-(2,5-dihydroxybenzoyl)-N2-(4-methylphenylsulfonyl)hydrazine are more safe than reference 5-fluorouracil. In silico drug relevant properties proposed that all compounds have high to moderate drug-likeness scores. Accordingly, these derivatives can be potential leads for development of potent antimicrobial and antioxidant agents.Graphical abstract

Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives

New quinoline compounds comprising pyrazole scaffold through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity. Eight compounds (5c, 11b,c, 12c, 14a,b, 20a and 21a) were found to exhibit promising anti-inflammatory profiles in acute and sub-acute inflammatory models. They were screened for their ulcerogenic activity and none of them showed significant ulcerogenic activity comparable to the reference drug celecoxib and are well tolerated by experimental animals with high safety margin (ALD50 > 0.3 g/kg). Compounds 5c, 11b,c, 12c, 14a,b, 20a and 21a showed significant in vitro LOX inhibitory activity higher than that of zileuton. In vitro COX-1/COX-2 inhibition study revealed that compounds 12c, 14a,b and 20a showed higher selectivity towards COX-2 than COX-1. Among the tested compounds, 12c, 14a and 14b showed the highest inhibitory activity against COX-2 with an IC50 values of 0.1, 0.11 and 0.11 μM respectively. The docking experiments attempted to postulate the binding mode for the most active compounds in the binding site of COX-2 enzymes and confirmed the high selectivity binding towards COX-2 enzyme over COX-1.