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A series of sorafenib derivatives with a 3-arylacryloyl hydrazide unit were designed and synthesized, and their anti-proliferative activity against human cancer cell lines (ACHN, HCT116, MDA-MB-231) were evaluated by MTT assay. Most of the synthesized compounds showed superior or similar cytotoxicity against the selected cell lines to the control sorafenib. Among these derivatives, compounds 8a, 8h, 8l, 8m, 11a and 11b showed potent anti-proliferative activity. Compounds 8h and 8m were selected for further evaluation of biological activity against more cancer cell lines. And oral administration of sorafenib analogue 8h at the same dose of sorafenib (30 mg/kg) in the pancreatic cancer Capan2 and Mia-PaCa2 xenograft models in nude mice showed tumour growth inhibition of 60.98 and 54.59 %, respectively, which is similar to the positive control sorafenib.

Chromone, imidazolidinedione, thiohydantoin and 2,4-thiazolidinedione structures are known to be cytotoxic to cancer cells. In this study, biological activities of previously synthesized 18 chromonyl-2,4-thiazolidinediones/imidazolidinediones/thiohydantoins were tested by sulforhodamine B assay in five liver and one breast cancer cell lines. It was shown that a hybrid chromonyl thiohydantoin derivative C9 was able to significantly suppress the proliferation of the liver cancer cell lines which are very resistant to anticancer drugs. According to 50% growth inhibition concentrations of C9, well differentiated hepatocellular carcinoma cell line Huh7 and breast adenocarcinoma cell line Mcf7 cells are found to be highly sensitive to C9 with IC50 values between 4.9–5.2 µM. Poorly differentiated human liver cancer cell line Snu449 is found to be the most resistant to C9. Further studies show that C9 causes morphological changes in Snu449 cells. However, it does not induce significant senescence response or cell cycle arrest. On the other hand, Huh7 cells are found to be arrested in G2/M phase of the cell cycle after 24 and 72 h treatment. In conclusion, a novel chromonyl thiohydantoin hybrid molecule effectively stops or slows down the proliferation of well-differentiated hepatocellular carcinoma cells that exist in primary tumors.

To develop a lead anti-diabetic compound, a series of 21 novel quinazoline derivatives have been synthesized and screened against α-glucosidase. The binding mode of the compounds at the active site of α-glucosidase was explored using Glide docking method. The binding model suggests one to four hydrogen bonding interactions between quinazoline derivatives and α-glucosidase. 6-Bromo-2-cyclopropyl quinazoline-4(3H)-one has been modified by C–C cross coupling to obtain nine different aryl scaffolds. These scaffolds further modified at C-4 position using amidation method to generate 21 compounds. Based on the interaction profile and docking score, all these compounds were selected for in vitro enzymatic screening. Seven of the thirty six compounds showed <20 µM activity against α-glucosidase and among these, compound 6f showed the highest inhibition, with an IC50 of 3.4 µM. In silico analysis was utilized to evaluate the diversity of the set of compounds against shape space, and relevant drug-like properties.

A new series of imidazo[2, 1-b]thiazole-based chalcone derivatives were designed, synthesized, and tested for their anticancer activities. Firstly, the cytotoxic ability of the compounds was tested on three different types of cancer cells, namely colorectal adenocarcinoma (HT-29), lung carcinoma (A-549), breast adenocarcinoma (MCF-7), and mouse fibroblast cells (3T3-L1) by XTT tests. Afterwards, further anticancer activity studies with the compound 3j having the lowest IC50 and highest SI values were performed on MCF-7 cells. XTT results revealed that all the test compounds exhibited much higher cytotoxic activity on the cancer cells than that of normal 3T3-L1 cells. Among the compounds, 3j especially stood out with its IC50 (9.76 µM) and SI (14.99) values on MCF-7 cells. Flow cytometry analysis proved that 3j-treated MCF-7 cells was resulted in the mitochondrial membrane depolarization, multicaspase activation, and ultimately apoptosis. Additionally, in silico molecular docking approaches were carried out to confirm the experimental observations and investigate the efficacy of the compound 3j. The interactions of 3j on DNA dodecamer and caspase-3 were investigated by molecular docking studies. Based on these interactions, the active amino acids in the binding site were determined and their free binding energies (ΔGBind) were calculated.

One of the members of a class of medications is cimetidine that is called H2-receptor antagonist or H2 blockers. Cimetidine reduced the amount of acid secreted by the lining cells of the stomach. It is commonly used in treatment of gastro-esophageal reflux disease and peptic ulcer disease. In this study, the cimetidine’s tautomers stability, structural data, HOMO, LUMO orbitals (energies and shapes), ΔΕ HOMO–LUMO gaps, ultraviolet–visible data and graphs, dipole moments, Mulliken charges, thermodynamic and kinetic stabilities in aqueous media as a biological solvent, and some of the different media (vacuum, H2O, EtOh, and dimethyl sulfoxide) have investigated for the tautomers of cimetidine by density functional theory-B3LYP/6-31G* method. The ultraviolet–visible experimental results of cimetidine were also compared with the theoretical density functional theory-B3LYP/6-31G* calculations. The results of this study have presented that the probability of the compatibility and adaptability of which imetidinetautomer (T1–T6) should be better than the other tautomers to interact with the H2-receptor pattern and the structural map.

Xanthine and its derivatives have been a great area of interest for the development of potent bioactive agents. In this study, two synthesis routes have been developed for 1,3,8-tri substituted xanthine derivatives. The synthesis routes exploits “xanthine” as precursor molecule as it represents maximum unsubstituted sites for maximum possible substitutions. This study divulged the reactivity pattern of three –NH groups at N1, N3 and N7 position of xanthine in the order of N7 > N3 > N1, which helped in carrying out regio-selective N-alkylation reaction at different –NH sites of xanthine. Selective protection and selective deprotection at N3 and/or N7 sites of xanthine were the key strategies for developing two synthesis schemes. Eight newly synthesized compounds C1-8 were evaluated for their biological activity against Phosphodiesterase 9A. All the compounds were found to be promising inhibitors. To gain further insight for mode of interaction with Phosphodiesterase 9A, these compounds were subjected to docking studies. The present study provides insight into the potential of ‘xanthine’ to contribute to the structural diversification of xanthine derivatives in the drug development process. Xanthine based chemical synthesis is shown to be a cost effective, fast, and highly productive method. This work can be extrapolated to find various selective xanthine based inhibitors targeting other enzymes.

Diabetes mellitus is a major metabolic disorder affecting a huge population all over the world. The aim of the current study was to validate the folkloric use of Artemisia indica as an antidiabetic plant by using the isolated compound carnosol from the chloroform fraction of Artemisia indica in streptozotocin-induced diabetes mellitus in rats. The antidiabetic activity-guided isolation of the chloroform fraction of Artemisia indica linn (Asteraceae) led to the isolation and characterization of carnosol. Carnosol was tested for its possible antidiabetic potential in streptozotocin [50 mg/kg. intra peritoneal (i.p)]-induced diabetic Sprague Dawley rats. Blood glucose level, body weight, serum lipid profile and activities of liver enzymes and effects on histopathological parameters were determined. A daily oral dose of carnosol (1–100 mg/kg b.w) for 15 days caused a significant reduction in blood glucose level, which was comparable to the standard antidiabetic drug, glibenclamide (0.5 mg/kg, p.o). Carnosol also showed reduction in triglycerides, total cholesterol, and low density lipoproteins (LDL) as well as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase and serum creatinine level in diabetic rats. Furthermore, in histopathological studies, carnosol reversed streptozotocin-induced changes in the pancreatic islets of Langerhans and caused regeneration and restored the integrity of pancreatic islets of Langerhans which may be responsible for its antihyperlgycemic effect. In conclusion, carnosol possesses hypoglycemic, antihyperlipidemic and useful protective effects on the liver and renal functions in diabetic rats, which suggests that the antidiabetic activity of Artemisia indica may be due in part to carnosol.

A comprehensive SAR study of a putative TLR 3/8/9 agonist was conducted. Despite the excitement surrounding the potential of the first small molecule TLR3 agonist with a compound that additionally displayed agonist activity for TLR8 and TLR9, compound 1 displayed disappointing activity in our hands, failing to match the potency (EC50) reported and displaying only a low efficacy for the extent of stimulated NF-κB activation and release. The evaluation of >75 analogs of 1, many of which constitute minor modifications in the structure, failed to identify any that displayed significant activity and none that exceeded the modest activity found for 1.

Some new 1H-benzo[b]xanthene and 4H-benzo[g]chromene derivatives of N-allyl quinolone were efficiently synthesized via microwave-induced one-pot three component reaction of N-allyl quinolones, 2-hydroxy-1,4-naphthoquinone and cyclic β-diketones/malononitrile, and iso-propylcyanoacetate in the presence of catalytic amount of ceric ammonium nitrate under solvent-free condition. This methodology allowed us to achieve the desired products in excellent yields in a very short time without the use of solvent. The % atom economy was calculated for all the newly synthesized compounds and found in the range of 92–96 %. Titled derivatives were elucidated by 1H NMR, 13C NMR, FT-IR, elemental analysis, and mass spectral data as well as tested against a panel of pathogenic strains of bacteria and fungi using by microdilution minimum inhibitory concentration method. The structural activity relationship analysis demonstrated that electronic influence and lipophilicity of different groups make much difference in the antimicrobial potency.

A number of imidazo[1,2-a]pyridine derivatives were selected and investigated in relation to anti-parasitic (Trichomonas vaginalis) activity. After treatment with derivatives, biological activity was assessed by determination of the in vitro viability of cell cultures, using alamar blue as a metabolic indicator. A good correlation was found between the anti-parasitic activity and the partition coefficient log P determined experimentally on the tested compounds, which explained up to 84% of the measured activity. A favorable interval (0.9 ± 0.3 log P) was found for optimum biological response.