RATIONAL DESIGN OF ANTIBACTERIAL THIENOPYRIMIDINES BY 2D-QSAR STUDY

QSAR studies were performed on a set of 43 analogs of thienopyrimidine using V-Life Molecular Design Suite (MDS 3.5) QSAR plus module by using Multiple Linear Regression (MLR) and Partial Least Squares (PLS) Regression methods against a gram positive (S.aureus) and a gram negative (E.coli) bacteria. MLR method has shown a very promising prediction results in both S.aureus and E.coli. QSAR model was generated by a training set of 34 molecules with correlation coefficient (r2) of 0.9849, 0.8719, significant cross validated correlation coefficient (q2) of 0.8881, 0.7811 and F test of  40.4301, 40.4768 respectively. In the selected descriptors, alignment independent descriptors such as T_C_C_7, T_N_O_3, T_2_N_1, T_N_O_1, T_O_O_7 and T_N_Cl_4 were the most important descriptors in predicting antibacterial activity

Synthesis, spectroscopy and X-​ray crystal structure of 9-​methyl-​3-​(2-​thienyl)​thieno[3,​2-​e]​[1,​2,​4]​triazolo[4,​3-​c]​pyrimidine-​8-​carboxylic acid ethyl ester

The synthesis of the target compd. was achieved by a reaction of 4-​cyano-​5-​[(ethoxymethylene)​amino]​-​3-​methyl-​2-​thiophenecarboxylic acid Et ester with 2-​thiophenecarboxylic acid hydrazide. The product thus obtained was confirmed by elemental anal., IR, 1H-​NMR, 13C-​NMR and X-​ray crystal structure anal. [i.e., 9-​methyl-​3-​(2-​thienyl)​thieno[3,​2-​e]​-​1,​2,​4-​triazolo[4,​3-​c]​pyrimidine-​8-​carboxylic acid Et ester]​. There are two independent mols. in the asym. unit exhibiting intermol. C-​H...N, C-​H...O interactions with addnl. π-​π interaction that further helps in stabilizing the supramol. structure

Crystal and Molecular Structure of 7-Methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4[3H]one

X-ray characterization of 7-methyl-5,6,7,8-tetrahydro[1]benzothieno [2,3-d]pyrimidin-4[3H]one is described. The compound crystallizes in the monoclinic space group P21/c with a=7.0013(2)Å, b=8.3116(3)Å, c=18.374(6)Å, β=91.746(2)°, V=1068.76(6)Å3, z=4. The structure was solved using the direct method and refined to reliability R-factor of 0.0639 using 3180 independent reflections The crystal structure is further stabilized by intermolecular C-H...N, N-H...N C-H...O, N-H...O, and π-π interactions

Synthesis, characterization and antimicrobial activity of benzo[<i>d</i>]isoxazo-3-yl-(N-4-oxo-2-phenylthiazolidin-3-yl)acetamide derivatives

560-566In the present study we have synthesized a novel series of benzo[d]isoxazo-3-yl-(N-4-oxo-2-phenylthiazolidin-3-yl)acetamides 5a-j by the condensation of benzo[d]isoxazol-3-acetohydrazides 3a-b with various aromatic aldehydes in the presence of catalytic amount of acetic acid followed by treating the intermediate benzo[d]isoxazol-3-yl acetic acid arylidine hydrazides 4a-j with thioacetic acid in presence of anhydrous zinc chloride in DMF. The structures of the newly synthesized compounds have been well established by spectral and elemental analysis. Further, the synthesized compounds have been screened for their in vitro antibacterial assayagainst both gram positive and gram negative bacterial strains and the results are compared with the standard antibiotic drug Streptomycin using micro dilution method. The present study has revealed that the compounds containing −NO2 and −F groups show enhanced antibacterial activity

Synthesis and in vitro anticancer activity of 6-chloro-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives: molecular docking and interaction with bovine serum albumin

A novel series of 6-chloro-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives were synthesized. Structure of the newly synthesized compounds was established by their analytical and spectroscopic data. The title compounds were evaluated for their anticancer activity against human breast cancer (T-47D) and lung cancer (NCI-H226) cell lines. Effects of compounds on the cell morphology of these cell lines were studied. Among the series of compounds tested, 6-chloro-7-methyl-2-(4-((2-(piperidin-1-yl)ethylamino)methyl) phenyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one [MTDP4(9)] exhibited good anticancer activity against both cell lines. Further, the binding interaction of [MTDP4(9)] with bovine serum albumin has been investigated by UV, fluorescence and molecular docking studies

Exploring the potential of newly synthesized 4-methyl-6-morpholino-pyrimidine derivatives as antiproliferative agents

In view of exploring the potential of pyrimidine derivatives as anticancer agents, a series of 4-methyl-6-morpholinopyrimidine derivatives was synthesised and characterised by NMR (H-1 & C-13), SC-XRD and mass spectral analysis. The in vitro anticancer activity of these compounds was investigated using different human cancer cell lines, namely HeLa (cervix), NCI-H460 (lung), MCF-7 (breast), HepG2 (liver) and IMR-32 (brain). Compounds 4c and 5h exhibited potent anticancer activity in a dose-dependent manner as compared to other derivatives, with IC50 values of 5.88 +/- 1.22 and 6.11 +/- 2.12 mu M on HeLa and NCI-H460, cells respectively. The inhibitory effect of 4c and 5h on cancer cell proliferation was shown to be a consequence of reactive oxygen species (ROS) generation and subsequent induction of cellular apoptosis, as evidenced by an increase in hypodiploid (subG1) population, early apoptotic cell population, caspase-3/7 activity, loss of mitochondrial membrane potential and degradation of nuclear DNA. Furthermore, molecular docking studies revealed that 4c and 5h compounds bind to the ATP binding pocket of the mammalian target of rapamycin (mTOR). Based on our results, we conclude that 4-methyl-6-morpholinopyrimidine derivatives prevent cancer cell proliferation by inducing apoptosis and thus have potential to be further explored for anticancer properties

In silico binding affinity studies of N-9 substituted 6-(4-(4-propoxyphenyl)piperazin-1-yl)-9H-purine derivatives-Target for P70-S6K1 & PI3K-δ kinases

P70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl) piperazin-1-yl)-9H-purine derivatives for their inhibitory properties with the above kinases. We have used an in silico docking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7 kcal/mol with P70-S6K1 kinase & −17.2 kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114). Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated by in vitro and in vivo experiments for further validation

Synthesis and antimicrobial activity of novel sulfides and sulfones of methylene-bridged benzisoxazolylimidazo[2,1-<i>b</i>][1,3,4]thiadiazoles

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Orange to red emissive aldehyde substituted donor-π-acceptor phenothiazine derivatives: Optoelectronic, DFT and thermal studies

A new class of probes was synthesized using a simple and efficient synthetic protocol. These compounds (PTZ-6(a-e)) have the phenothiazine (PTZ) moiety as the electron donor (D) and substituted aldehydes along with the acrylonitrile group, which acts as the electron acceptor (A), thus making D-π-A push-pull system. The structures of the newly synthesized series of small organic target molecules PTZ-6(a-e) were investigated and confirmed by spectros-copic techniques. The optical/solvatochromic properties were studied in detail by UV-vis absorption and fluorescence spectroscopy, because the molecules have shown good solubility in organic solvents. The density functional theory (DFT) model with the CAM-B3LYP function is utilized to study the photophysical properties of the probes, as these probes exhibited orange-to-red emission. Optical band gap values ranged from 2.32 to 2.50 eV, and these probes exhibited good thermal stability with a melting temperature of 136 to 198 °C and a T5d temperature range from 335 to 354 °C. The cyclic voltammetry study confirms that the Eoxonset values of the target compounds are 0.80 eV. The quantum yields (Φ) of the probes are measured experimentally in ethanol and the Stokes shifts are observed to be in the range of 4846-9430 cm-1. The results displayed that novel (D-A-D) chromophores could play an important role in organic optoelectronics