Letters in Drug Design & Discovery - Volume 11, Issue 4, 2014

Cytotoxic activity of four O,O'-dialkyl esters of ethylene-bis(S)-leucine [(S,S)-ethylenediamine-N,N’-di-2-(4- methyl)pentanoic acid] dihydrochlorides, R2edda-type esters L1.2HCl–L4.2HCl (alkyl = Et, n-Pr, n-Bu, and n-Pe, respectively), and corresponding palladium(II) (1–4) and platinum(II) (5–8) complexes against MDA-MB-361, MDA-MB-453 (human breast cancer), Jurkat (T-leukemia) and K562 (chronic myelogenous leukaemia) c Read More

Two series of new ionone alkaloid derivatives were synthesized and evaluated for antitumor invasive activities in human MDA-MB-231 breast cancer cells. The structures of derivatives were elucidated by 1H, 13C NMR and mass spectrometric methods. Ionone alkaloid derivatives 1a, 1c, 1d, 4i, 4j and 4k revealed significant inhibitory effects on the invasion of MDA-MB-231 cells in invasion assay, and compound 4j bearing a 4-fluoro Read More

Carbonic anhydrases XIV (CA XIV) is responsible for health issue and a therapeutic target of many disorders like epilepsy, and retinopathy. Here we described the first pharmacophore model for human CA XIV to identify the new scaffolds compounds. Hypotheses 1, with the highest cost difference, best correlation coefficient as well as the lowest RMSD, was validated by test set and Fischer method. Then, Hypotheses 1 wa Read More

A novel series of 2,5-disubstituted-1,3,4-oxadiazole analogs (4a-j) was synthesized starting from 2-aminopyrimidine. A computational study was carried out for the molecular properties prediction and none of the compounds violated Lipinski “Rule of 5”. The structures of the compounds were confirmed on the basis of their spectral data and the purity of the compounds was checked by elemental analysis. Some of the compou Read More

Neuraminidase (NA) is a glycoprotein found on the surface of influenza A virus that is used for releasing new progeny of virions by cleaving the terminal sialic acid residue from the surface of infected cells. Therefore, NA is an interesting potential target to design promising NA inhibitiors to serve as antiviral agents for preventing viral propagation. In this study, a data set of 61 H1N1 neuraminidase inhibitors of influenza A vir Read More

The antiproliferative activities of new substituted tetrahydroisoquinolines (THIQs) are described. Their cytotoxicities against Ishikawa human endometrial cell line were determined after 72 h drug expose employing Celtiter-Glo assay at concentrations ranging from 0.01 to 100,000 nM. The antiproliferative activities of the compounds understudy were compared to tamoxifen (TAM). In-vitro results indicated that most of the c Read More

We consider dialkyl esters of 5-aminosulfonylisophthanoate-based compounds in our efforts to determine factors involved in determining the overall inhibitory activity against estrone sulfatase (ES). We propose that the weak inhibition observed is due to the increased electron density in the area of the phenyl ring close to the sulfamate moiety.

Protein tyrosine phosphatase 1B (PTP1B) is a well known drug target for the treatment of type 2 diabetes mellitus (T2DM). Diverse inhibitors have been reported in literature that inhibit PTP1B. We have reported 2-substituted benzoxazole class of In PTP1B inhibitors earlier. Present work describes 2-substituted benzothiazole compounds as PTP1B inhibitor as an extension of our previous study. Compound 23c, a disubstitut Read More

The present study deals with successful utilization of both correlation and classification techniques for the development of diverse models for the prediction of dual mTOR and PI3Kα inhibitory activities using a dataset comprising of 39 analogues of 4-morpholinopyrrolopyrimidines. Decision tree, random forest, moving average analysis (MAA) and multiple linear regression (MLR) were used to develop models for mTOR and PI Read More

A series of pyrazole analogues of curcumin were synthesized and investigated for in vitro and in silico antimicrobial activity. The structures of newly synthesized compounds were ascertained on the basis of their analytical and spectral profiles. The compounds were subjected to molecular docking studies for the inhibition of the enzyme glucosamine-6- phosphate synthase [GlcN-6-P]. The autodock program 4.2 was employe Read More

A cost-effective and improved process was developed for the synthesis of the antiviral drug Valacyclovir hydrochloride 1. The process involves the Streglich condensation between 4 and 6 to obtain N-Phthalimide-L-Valine ester 5, which was deprotected by using 40% monomethylamine Overall, the chemistry has been developed and used to prepare Valacyclovir drug 1 in an overall yield of 61 %.

A series of 6-alkoxy-2-(4H-1,2,4-triazol-4-yl)benzothiazoles was synthesized and evaluated for their anticonvulsant activity using the maximal electroshock (MES) method. Interestingly, all of the compounds prepared showed long duration of protection effect in the MES screens. And none of them, except compounds 4b and 4d, showed any neurotoxicity at dose of 300 mg/kg. Compound 4c was considered as the most pro Read More

Background: Anesthesiologists can choose from several generic sevoflurane products available. Although both original and generic products contain high-purity sevoflurane, their minor components appear to be subtly different. We previously reported that original sevoflurane products contain a greater amount of water and smaller amount of related substances than generic sevoflurane. Since then, the manufacturer h Read More

As a part of our ongoing studies in developing new derivatives as dual antibacterial/antifungal agents, we describe the synthesis of novel amino substituted benzofuroxan derivatives. These compounds were tested for their antifungal activity against various strains. It is shown that their antimicrobial and antifungal activities depend on the structure of the amino moiety, on the position and on the nature of the substituent Read More

Flexible hydroquinone-based compounds were previously proposed as potential mutant-resistant NNRTIs inhibitors, however, experimental or computational evidences did not support this proposal. Herewith, using an integrated in-silico computational approach involving de-novo drug design, structure-based virtual screening (SBVS), molecular dynamics simulations and post-dynamic per-residue binding energy decomp Read More