Iron mediated reductive cyclization/oxidation for the generation of chemically diverse scaffolds: An approach in drug discovery.

Chemically diverse scaffolds represent a main source of biologically important starting points in drug discovery. Herein, we report the development of such diverse scaffolds from nitroarene/ nitro(hetero)arenes using a key synthetic strategy. In a pilot-scale study, the synthesis of 10 diverse scaffolds was achieved.

Correction: Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway).

Correction for 'Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway)' by C. Ganesh Kumar et al., Nanoscale, 2015, 7, 18738-18750.

Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity, CoMFA and CoMSIA studies.

A series of novel furo[2,3-b]pyridine-2-carboxamide 4a-h/pyrido[3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives 5a-p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with α-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo[2,3-b]pyridine-2-carbohydrazide Schiff's bases 7a-h and pyrido [3',2':4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a-h starting from furo[2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a-h, 5a-p, 7a-h and 8a-h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293).

Studies on synthesis of novel pyrido[2,3-d]pyrimidine derivatives, evaluation of their antimicrobial activity and molecular docking.

A series of novel pyrido[2,3-d]pyrimidine derivatives 6 were prepared starting from 2-amino-3-cyano-4-trifluoromethyl-6-phenyl pyridine 3 via Grignard's reaction, cyclization followed by coupling with aliphatic and cyclic amines. All the compounds 6 were screened for antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition activity as well as antifungal and minimum fungicidal concentration (MFC) activities. Among the screened compounds, the compounds 6e, 6f, and 6m which showed exhibiting promising activity have been identified.

Comparative study of cyto- and genotoxic potential with mechanistic insights of tungsten oxide nano- and microparticles in lung carcinoma cells.

The exigency of semiconductor and super capacitor tungsten oxide nanoparticles (WO NPs) is increasing in various sectors. However, limited information on their toxicity and biological interactions are available. Hence, we explored the underlying mechanisms of toxicity induced by WO NPs and their microparticles (MPs) using different concentrations (0-300 μg ml ) in human lung carcinoma (A549) cells.

Synthesis and Bioevaluation of Quaternary Centered 3-hydroxy-3 (alkynyl)indolin-2-one Derivatives as Potential Cytotoxic Agents and Akt Kinase Inhibitors.

Background: Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality.

Objective: In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity.

Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis.

A series of novel alkyl amide functionalized 2,3-pyrazole fused quinoline derivatives 5, 6 and 7 have been prepared starting from quinoline-2(1H)one 1 in a series of steps. All the final products were screened for antibacterial activity, the promising lead compound 5r was identified with MIC values ranging between 3.9 and 7.

Design, synthesis and evaluation of novel pyrazolo-pyrimido[4,5-d]pyrimidine derivatives as potent antibacterial and biofilm inhibitors.

An efficient four-component reaction of 6-amino-1,3-dimethyluracil, N,N-dimethylformamide dimethylacetal, 1-phenyl-3-(4-substituted-phenyl)-4-formyl-1H-pyrazoles and aromatic amines was conducted in the presence of [Bmim]FeCl ionic liquid as a promoting medium. This strategy provided a convenient route without any additional catalyst or metal salt under mild conditions. All the synthesized pyrazolo-pyrimido[4,5-d]pyrimidines derivatives were evaluated for their antibacterial, minimum bactericidal concentration (MBC), biofilm inhibition, intracellular ROS accumulation and protein leakage activities.

Synthesis of Novel Fatty Substituted 4-methyl-2HChromen-2-one via Cross Metathesis: Potential Antioxidants and Chemotherapeutic Agents.

A series of novel fatty substituted 4-methyl-2H-chromen-2-one (coumarins) were synthesized by employing cross metathesis, a key step in the synthesis. The antioxidant activities of the title compounds were compared with the commercial antioxidants, namely butylated hydroxy toluene (BHT) and α-tocopherol, glycosidic and other substituted 4-methyl-2H-chromen-2-ones. Among the different 4-methyl-2H-chromen-2-ones, the glycosidic substituted 4-methyl-2H-chromen-2-ones was excellent, while those with aliphatic fatty acid chain and hydroxyl substitutents were good.

Synthesis of novel ethyl 2,4-disubstituted 8-(trifluoromethyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate derivatives as promising anticancer agents.

A series of novel pyrido[2',3':3,4] pyrazolo[1,5-a]pyrimidine derivatives 6-9 were prepared in single step starting from 3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 5 on reaction with symmetrical and unsymmetrical aliphatic and aromatic 1,3-diketones/α,β unsaturated ketones/α,β unsaturated keto ethers under conventional method. All the final compounds 6a-c, 8a-b and 9a-l were screened for anticancer activity against five human cancer cell lines such as PC-3 (CRL-1435), MDA-MB-231 (HTB-26), Hep G2 (HB-8065), HeLa (CCL-2) and normal HUVEC (CRL-1730). Compounds 8a, 9f and 9k which showed promising anticancer activity have been identified.

Synthesis and biological evaluation of ricinoleic acid-based lipoamino acid derivatives.

A series of novel ricinoleic acid based lipoamino acid derivatives were synthesized from (Z)-methyl-12-aminooctadec-9-enoate and different l-amino acids (glycine, alanine, phenyl alanine, valine, leucine, isoleucine, proline and tryptophan). The structures of all the prepared compounds were characterized by H NMR, C NMR and mass spectral studies. The title compounds were evaluated for their antimicrobial and anti-biofilm activities.

Synthesis of novel nicotinohydrazide and (1,3,4-oxadiazol-2-yl)-6-(trifluoromethyl)pyridine derivatives as potential anticancer agents.

A series of novel nicotinohydrazide derivatives 6a-g and 1,3,4-oxadiazole functionalized pyridine derivatives 7a-k and 8a-d were prepared in series of steps. All the compounds were screened for cytotoxicity against HeLa (cervical), DU145 (prostate), HepG2 (liver) and MBA-MB-231 (breast) human cancer cell lines. Compounds 6h, 6i, 7d, 7h, 7i and 8b which showed promising cytotoxicity at <15μM concentration have been identified.

Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents.

A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule.

An efficient one-pot synthesis of thiochromeno[3,4-d]pyrimidines derivatives: Inducing ROS dependent antibacterial and anti-biofilm activities.

An efficient synthesis of thiochromeno[3,4-d]pyrimidine derivatives has been achieved successfully via a one-pot three-component reaction of thiochrome-4-one, aromatic aldehyde and thiourea in the presence of 1-butyl-3-methyl imidazolium hydrogen sulphate [Bmim]HSO4. This new protocol has the advantages of environmental friendliness, high yields, short reaction times, and convenient operation. Furthermore, among all the tested derivatives, compounds 4b and 4c exhibited promising antibacterial, minimum bactericidal concentration and anti-biofilm activities against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS16 MTCC 2940 and Bacillus subtilis MTCC 121.

An expeditious four-component domino protocol for the synthesis of novel thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidine derivatives as antibacterial and antibiofilm agents.

An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via [Bmim]HSO4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5H)-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular NH bond activation followed by CS bond formation leading to highly functionalized thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidines. The ionic liquid operates efficiently under mild conditions.

Total synthesis and in vitro bioevaluation of clavaminols A, C, H & deacetyl clavaminol H as potential chemotherapeutic and antibiofilm agents.

A highly concise and expedient total synthesis of bioactive clavaminols (1-4) has been executed using commercially available achiral compound decanol. The synthetic strategy relied on trans-Wittig olefination, Sharpless asymmetric epoxidation, regioselective azidolysis and in situ detosylation followed by reduction as key reactions with good overall yield. Based on biological evaluation studies of all the synthesized compounds, it was observed that the clavaminol A (1) exhibited good cytotoxicity against DU145 and SKOV3 cell lines with IC50 value of 10.

Design, synthesis and in vitro biological evaluation of short-chain C12-sphinganine and its 1,2,3-triazole analogs as potential antimicrobial and anti-biofilm agents.

A conceptual synthetic approach of short-chain C12-sphinganine 1 and a small library of its 1,2,3-triazole analogs 2(a-f) has been accomplished using the commercially available and inexpensive 10-undecenoic acid as a starting material. Miyashita's C-2 selective endo mode azidolysis and Huisgen click reaction was employed for the synthesis of the designed analogs. Based on biological evaluation studies of all the synthesized compounds, it was observed that, (2S,3R)-2-(4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)dodecan-1,3-diol (2b) exhibited promising antimicrobial and antifungal activities.

Design, synthesis and biological evaluation of diaziridinyl quinone isoxazole hybrids.

A series of novel diaziridinyl quinone isoxazole hybrids (9a-9j) were synthesized starting from 2, 5-dimethoxy acetophenone 1 via Claisen reaction, cyclisation, alkoxy carbonylation, hydrolysis, oxidation and aziridine insertion. All the compounds were screened for antimicrobial, anti-biofilm and cytotoxic activities. Among the screened compounds, the compound 9h showed good antibacterial and anti-biofilm activities with MIC value of 3.

Synthesis, characterization, antimicrobial and biofilm inhibitory studies of new esterquats.

Novel esterquats (monoesterquats and diesterquats) were synthesized from 11-bromo undecanoic acid (11-BUA) and different alkyl amines. The prepared compounds were characterized by FT-IR, (1)H NMR, (13)C NMR and mass spectral analysis. 11-BUA was converted into methyl 11-bromo undecanoate which was further converted into amine ester (amine monoester and diester) by reacting with different aliphatic amines (hexyl, dodecyl, octadecyl, dioctyl and dicyclohexyl amine).

Synthesis of dihydrosterculic acid-based monoglucosyl diacylglycerol and its analogues and their biological evaluation.

In the present study, Lactobacillus plantarum glycolipid (GL1) molecule in β-configuration and its fatty acid analogues were synthesized using trichloroacetimidate methodology. The β-configuration of the GL1 molecule was unambiguously assigned by NMR studies using 2D-ROESY (NOE) and J-coupling analysis. Dihydrosterculic acid was synthesized using Furukawa's reagent and the selective esterification of dihydrosterculic acid at C-3 position of glycerol was achieved with EDC-HCl at 0 °C.

Synthesis of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives and their biological evaluation.

A series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at 60°C.

Synthesis of novel trifluoromethyl substituted furo[2,3-b]pyridine and pyrido[3',2':4,5]furo[3,2-d]pyrimidine derivatives as potential anticancer agents.

A series of novel trifluoromethyl substituted furo[2,3-b]pyridine and pyrido[3',2':4,5]furo[3,2-d] pyrimidine derivatives 3a-b, 6a-k, 9, 10a-b, 11a-c and 12a-c were prepared from 2-carbethoxy-3-amino-6-trifluoromethyl furo[2,3-b]pyridine 1 under different set of conditions. Compounds functionalized with oxadiazole 11a-c were also prepared from 2-carbohydrazide-3-amino-6-trifluoromethyl furo[2,3-b]pyridine 4. All the final products were screened for anticancer activity against four human cancer cell lines such as Neuro-2a, Hela, A549 and COLO 205 as well as normal human lung cell line, IMR-90.

Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway).

The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses.

Synthesis and antimicrobial potential of nitrofuran-triazole congeners.

A series of 5-nitrofuran-triazole congeners were designed and synthesized by carrying out suitable structural modifications of the previously reported counterparts and were evaluated for their antimicrobial potential against both Gram-positive and Gram-negative bacterial strains. The compounds exhibited promising inhibition towards different Gram-positive pathogenic strains, while mild inhibitory effects were observed towards Gram-negative bacterial strains. Some of the compounds 9f, 9g, 9l and 9m were most active among the series, exhibiting a MIC value of 1.