Exploring QSAR of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists using FA and GFA techniques

QSAR of Antiproliferative Activity of N‐Substituted 2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles in Various Human Cancer Cells

“…20). Binding affinity of 1,3,4-thiadiazoles for the human adenosine A 3 receptor subtype is also a function of lipophilicity and Wang -Ford charges of atoms [45]. On the other hand, antiproliferative effect of compounds is connected with E LUMO or hardness (h).…”

Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?

“…(20)(21)(22) pK i ¼ 4:030 À 3:951ðAE2:415Þq 2 À 2:623ðAE2:136Þq 5 þ 2:441ðAE1:489Þq 7 À 0:275ðAE0:261Þ log P À where q x were the Wang-Ford charges of different atoms (x) of the analogues; I OBu À t is an indicator variable having a value 1 if tert-butyloxy group is present at thr R position, value 0 otherwise; I Me À Et is an indicator variable having value 1 if R ¼ methyl or ethyl, value 0 otherwise and f x represent factors loadings and have the character of correlation coefficients between the common factors and the variables. Another QSAR study for A 3 ARs was reported by Borghini et al, 116 who used a data set of thiazole and thiadiazole antagonist analogues (very similar to those studied by Bhattacharya et al 159 ) reported in the literature 17 and their affinity values were expressed as pK i , generated for displacement of specific where HACA _ 2 means total charge weighted HACA, HACA means hydrogen-acceptor charged surface area, and TMSA means total molecular surface area; RNH is the constitutional descriptor relative number of H atoms; MPCS is the minimum partial charge on a S atom; WNSA _ 3 is the total surface weighted PNSA and PNSA means partial negative surface area. Moreover, the results appear to furnish useful suggestions for the design of new ligands to act as antagonists for the adenosine A 3 receptors and confirm the results previously obtained by Bhattacharya et al 159 The model suggests the importance of small alkyl groups at the position R, since they increase the contribution coefficient of this descriptor RNH more than aromatic rings.…”

“…On the other hand, Bhattacharya et al reported another QSAR study 159 that involved the use of the same statistical techniques, descriptors and a data set of 30 thiazole and thiadiazole derivatives that are A 3 AR antagonists, previously published by Jung et al 17 (see Fig. 16) and their affinity values were expressed as pK i , generated for displacement of specific […”

Synthesis and Pharmacological Evaluation: Antimicrobial, Anti-Inflammatory, Analgesic, Ulcerogenic Properties of Several Bis-Heterocyclic Derivatives

“…Microbial infections cause pain and inflammation. In the current study, we have focused on thiadiazoles due to its versatile biological profile such as hypoglycemic (Avetisyan et al, 1981), anticancer (Parkanyi et al 1992), anti-inflammatory (Boschelli et al, 1993;Labanauskas et al, 2001;Schenone et al, 2001), anti-asthmatic (Bhattacharya et al, 2005), antihypertensive (Vio et al, 1989), antidepressant (Clerici et al, 2001), anxiolytic (Clerici et al, 2001), fungicidal (Chen and Hen, 2000; and antituberculosis (Foroumadi et al, 2001). On the other hand, esters of 1,1-cyclopropane dicarboxylic acid were found to possess important insecticidal activity (Ronald and Leland 1998).…”