Filanesib

Kinesin spindle protein (Eg5) has been widely studied, as an important target for developing chemotherapy drugs, due to its essential role in mitotic spindle formation in mitosis.In this study, we target a promising novel allosteric site involving α4 and α6 helixes, which is located 15 Å from the allosteric ispinesib site.An extensive 3D-Pharmacophore structure based virtual screening was conducted.Mol. docking was carried out to explore a library of com. mols.Eleven compounds were identified with diversity in their chem. scaffold.Biol. evaluation and MT ATPase assays revealed that compound 11 with scaffold N-(2- (2, 6 -dimethylphenoxy) phenyl) -3, 4-dihydro -3-oxo -2H-benzo[b][1,4]oxazine-6-carboxamide inhibits Eg5 activity at (IC₅₀ = 1.37 ± 0.15 μM).The chem. structure of compound 11 was confirmed by ¹H NMR and mass spectral data.The stability of compound 11 within the Eg5-ADP/ATP complex was investigated using mol. dynamic simulation technique.The free binding energy was calculated using MM/PBSA.

Hybrid mols. based on the 1,3,4-thiadiazole were always the choice of different researchers due to their significant application in medicinal as well as pharmaceutical application.In the present study, twenty analogs of 1,3,4-thiadiazole-bearing thiosemicarbazide moiety (1-20) were synthesized and screened for their anti-diabetic profile.The synthesized compounds were spectroscopically characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, and HREI-MS.Comparing the whole set of afforded compounds to the standard glimepiride drugs (16.01 ± 0.02 μM), the inhibition profiles against α-amylase ranged from 21.02 ± 0.08 to 54.08 ± 0.04 μM.Comparing synthetic analogs to normal glimepiride (IC50 = 14.06 ± 0.05 μM), the range of α-glucosidase activity was likewise variable, ranging from 18.04 ± 0.07 μM to IC50 = 51.05 ± 0.03 μM (against α-glucosidase).Compound 19 demonstrated high potency among the produced analogs since it had both ortho-nitro substitution at the aryl ring.The pattern of substitutions around the aryl ring was used for all analogs to determine the structure-activity relationship.In addition, a mol. docking study was conducted on the potent analogs to examine the interactions between the active residues of the targeted enzymes with the synthesized compoundThe synthesized mol. showed different types of interactions with amino acid.The outcome demonstrates that these compounds provide several essential interactions with the active sites of enzymes, hence strengthening their enzymic activity for the future prediction as drug competitors.