Novel adamantyl clubbed iminothiazolidinones as promising elastase inhibitors: design, synthesis, molecular docking, ADMET and DFT studies

Abstract

Structurally diverse adamantyl-iminothiazolidinone conjugates were synthesized, evaluated for elastase inhibition, and subjected to in silico ADMET prediction. The inhibition studies revealed compounds 5a, 5f, 5g, and 5h to show significant activity.

RETRACTED: In-silico modelling studies of 5-benzyl-4-thiazolinone derivatives as influenza neuraminidase inhibitors via 2D-QSAR, 3D-QSAR, molecular docking, and ADMET predictions

“…The six lead molecules which have passed the Lipinski rule of five ( Table 14 ) were further assessed with other drug-likeness filter rules such as the Ghose filter rule, Veber’s rule, Egan’s rule, and Muegge’s rule using the SwissADME web server as shown in Table 15 . Lipinski's criteria for drug-likeness include molecular weight (MW ≤ 500 g/mol), n-octanol/water distribution coefficient (Log P ≤ 5), number of hydrogen bond acceptors (nHA ≤10), and number of hydrogen bond donors (nHD ≤5) ( Ahmed et al., 2022 ; Chauhan et al., 2014 ). From Lipinski's table of the lead molecules in the data set, the Log P scores of the molecules are relatively close to 3 log mol/L (optimal limit) except for molecule 17 which is slightly above the optimal limit (0 < Log P < 3).…”

“…Some of the relevant computed ADMET parameters include human intestinal absorption (HIA), human colon adenocarcinoma cell lines (Caco-2) permeability, Madin−Darby Canine Kidney cells (MDCK) permeability, plasma glycoprotein (Pgp) inhibitor, plasma glycoprotein (Pgp) substrate, plasma protein binding (PPB), volume distribution (VD), blood-brain barrier (BBB) penetration, human cytochromes (CYP), clearance (CL), half-life (T1/2), AMES toxicity, carcinogenicity (Carc), eye irritation (EI), respiratory toxicity (RT) as shown in Table 16 . The Caco-2 cell permeability has been an important index for an eligible drug candidate which is associated with human intestinal absorption ( Ahmed et al., 2022 ). The lead compounds were considered to have proper Caco-2 cell permeability because their values are higher than the optimal score of 5.15 log cm/s.…”

Design, Synthesis, Kinetic Analysis and Pharmacophore-Directed Discovery of 3-Ethylaniline Hybrid Imino-Thiazolidinone as Potential Inhibitor of Carbonic Anhydrase II: An Emerging Biological Target for Treatment of Cancer

“…The synthesis of imino-thiazolidinone derivatives were carried out according to a Scheme 1 [ 25 ] synthetic approach. Using DCM as a solvent, substituted benzoic acids were transformed to matching acid chlorides.…”

Computational modelling studies of some 1,3-thiazine derivatives as anti-influenza inhibitors targeting H1N1 neuraminidase via 2D-QSAR, 3D-QSAR, molecular docking, and ADMET predictions

“…The computed value for HIA showed that the lead compounds have the probability of excellent absorption from the intestinal membrane. The Caco-2 cell permeability has been an important index for an eligible drug candidate which is associated with human intestinal absorption [46]. The lead compounds were considered to have proper Caco-2 cell permeability because their values are higher than the optimal score of − 5.15 log cm/s.…”

“…rule, Egan'rule, and Muegge's rule using the SwissADME Web server as shown in Table15. Lipinski's criteria for drug-likeness include molecular weight (MW ≤ 500 g/ mol), n-octanol/water distribution coefficient (Log P ≤ 5), number of hydrogen bond acceptors (nHA ≤ 10), and number of hydrogen bond donors (nHD ≤ 5)[45,46].…”