Synthesis and biological evaluation of novel benzenesulfonamide incorporated thiazole-triazole hybrids as antimicrobial and antioxidant agents.

A library of 20 novel benzenesulfonamide incorporating thiazole tethered 1,2,3-triazoles 1-4a-e was synthesized and screened for their antimicrobial, antioxidant, and cytotoxicity studies. Amoxicillin and fluconazole were used as reference antibacterial and antifungal drugs, respectively. Further, energies of frontier molecular orbitals were calculated for all the synthesized target compounds 1-4a-e to correlate electronic parameters with the observed biological results. Global reactivity descriptors, including highest occupied molecular orbitals-lowest unoccupied molecular orbitals energy gap, electronegativity, chemical hardness, chemical softness, and electrophilicity index, were also calculated for the synthesized molecules. All the tested compounds possessed moderate to excellent antibacterial potency; however, 3d and 4d exhibited the overall highest antibacterial effect (minimum inhibitory concentration [MIC] values 5-11 µM) while 2c showed the highest antifungal effect (MIC value 6 µM). Compound 3c exhibited the highest antioxidant activity with a % radical scavenging activity value of 95.12. The cytotoxicity of the compounds 1-4a-e was also checked against an animal cell line and a plant seed germination cell line, and the compounds were found to be safe against both the tested cell lines.

Novel benzenesulfonamide-bearing pyrazoles and 1,2,4-thiadiazoles as selective carbonic anhydrase inhibitors.

Two series comprising 20 novel benzenesulfonamides bearing thioureido-linked pyrazole 8 and amino-1,2,4-thiadiazole 10 were synthesized and assayed as human carbonic anhydrase (hCA) inhibitors against isoforms I and II as well as the tumor-associated isoforms IX and XII. Molecular modeling studies of some potent derivatives (8a, 8c, 10a, and 10c) were also performed against isoforms hCA I, II, and XII. Both the promising series of compounds were synthesized by using commercially available mtethyl ketones and sulfanilamide as the starting materials. Interestingly, this paper also reports a novel methodology for the synthesis of amino-1,2,4-thiadiazoles 10 using 3-amino isoxazoles and 4-isothiocyanatobenzenesulfonamide as reactants. The activity profile of all the newly synthesized compounds reveals that amino-linked 1,2,4-thiadiazoles 10 were better inhibitors of the cytosolic isoform, hCA I, as compared to thioureido-linked pyrazoles 8. Further, hCA II was strongly inhibited by nearly all the newly synthesized sulfonamides, while all the compounds were less effective as hCA IX and XII inhibitors compared to the standard drug acetazolamide. However, in terms of selectivity, compound 8e was found to be the most selective inhibitor of hCA II, which is the isoform associated with glaucoma, edema, altitude sickness, and epilepsy.

Benzenesulfonamide bearing imidazothiadiazole and thiazolotriazole scaffolds as potent tumor associated human carbonic anhydrase IX and XII inhibitors.

Two series of 20 novel heterocyclic compounds, imidazothiadiazoles (3a-3j) and thiazolotriazoles (4a-4j) bearing benzenesulfonamide moiety were synthesized in order to investigate the inhibition potential of both scaffolds against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). Against human isoform hCA I, compounds 3j, 4a-4c, and 4j showed better inhibition potential (Ki<100nM) than the standard drug acetazolamide (AZA). Against hCA II, all the compounds showed moderate inhibition with the exception of 3a which showed nearly two fold better profile compared to AZA. Against hCA IX, all the compounds showed moderate inhibitory potential than AZA, whereas against hCA XII, compounds 3a-3c showed better inhibitory potential compared to AZA.

Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII.

A series of pyrazolylpyrazolines was designed, synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against cytosolic human (h) isozymes hCA I and hCA II as well as transmembrane tumor associated isozymes, hCA IX and hCA XII. All the tested compounds exhibited an excellent CA activity profile against hCA I, hCA II and hCA XII when compared to the reference drug acetazolamide (AZA). Compounds 6d, 6f and 7a-7f have exhibited better inhibition profile against hCA XII (Ki = 0.47-5.1 nM) as compared with AZA (Ki = 5.7 nM) especially, compounds 6a, 7a, 7c and 7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds 6c, 6d, 7c and 7d (Ki = 1.1-1.7 nM) were many fold better inhibitors than AZA (Ki = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I.