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Background Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques (1H-NMR, 13C-NMR, IR, MS, and CHN). Results The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. Conclusion In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins. Electronic supplementary material The online version of this article (10.1186/s13065-018-0399-0) contains supplementary material, which is available to authorized users.

Background Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate (1) by using plant and microbial cultures. Results The biotransformation of ethynodiol diacetate (1) with Cunninghamella elegans and plant cell suspension cultures of Ocimum basilicum and Azadirachta indica is being reported here for the first time. Biotransformation of 1 with Cunninghamella elegans yielded three new hydroxylated compounds, characterized as 17α-ethynylestr-4-en-3β,17β-diacetoxy-6α-ol (2), 17α-ethynylestr-4-en-3β,17β-diacetoxy-6β-ol (3), and 17α-ethynylestr-4-en-3β,17β-diacetoxy-10β-ol (4) and a known metabolite, 17α-ethynyl-17β-acetoxyestr-4-en-3-one (5). The biotransformation of 1 with Ocimum basilicum included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17α-ethynyl-17β-acetoxyestr-4-en-3-one (5), 17α-ethynyl-17β-hydroxyestr-4-en-3-one (6), 17α-ethynyl-3 β-hydroxy-17β-acetoxyestr-4-ene (7) and 17α-ethynyl-5α,17β-dihydroxyestr-3-ene (8). Biotransformation of 1 with Azadirachta indica culture yielded compounds 5 and 6. Spectroscopic data of compound 8 is being reported for the first time. Structure of compound 6 was unambiguously deduced through single-crystal x-ray diffraction studies. Conclusion Biotransformation of an oral contraceptive, ethynodiol diacetate (1), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.

Background Green chemistry is a rapidly developing new field that provides us with a proactive avenue for the sustainable development of future science and technologies. Green chemistry uses highly efficient and environmentally benign synthetic protocols to deliver lifesaving medicines, accelerating lead optimization processes in drug discovery, with reduced unnecessary environmental impact. From this view point, it is desirable to use water instead of organic solvents as a reaction medium, since water is safe, abundant and an environmentally benign solvent. Results A convenient one-pot method for the efficient synthesis of the novel Zwitterion derivatives 4a-pvia a three-component condensation reaction of barbituric acid derivatives 1a,b, dimedone 2, and various aldehydes 3 in the presence of aqueous diethylamine media is described. This new approach is environmentally benign, with clean synthetic procedure, short reaction times and easy work-up procedure which proceeded smoothly to provide excellent yield (88-98%). The synthesized products were characterized by elemental analysis, IR, MS, NMR and CHN analysis. The structure of 4a was further confirmed by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic space group Pbca with α = 14.6669 (5) Å, b = 18.3084 (6) Å, c = 19.0294 (6) Å, α = 90°, β = 90°, = 90°, V = 5109.9 (3) Å3, and Z = 8. The molecules are packed in crystal structure by weak intermolecular C–H⋅ ⋅ ⋅O hydrogen bonding interactions. Conclusions An environmentally benign Aldol-Michael protocol for the synthesis of dimedone-barbituric derivatives using aqueous diethylamine medium is achieved.

Background The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application. Results A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3–9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and β-glucuronidase and α-glucosidase inhibitory activities. Compound 3 (IC50 = 56.26 ± 3.18 μM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50 = 105.9 ± 1.1 μM). Compounds 8a (IC50 = 13.2 ± 0.34 μM) and 8b (IC50 = 14.1 ± 0.28 μM) found as potent inhibitor of α-glucusidase several fold more active than the standard acarbose (IC50 = 841 ± 1.73 μM). Most promising results were obtained in β-glucuronidase enzyme inhibition assay. Compounds 5 (IC50 = 0.13 ± 0.019 μM), 6 (IC50 = 19.9 ± 0.285 μM), 8a (IC50 = 1.2 ± 0.0785 μM) and 9 (IC50 = 0.003 ± 0.09 μM) showed a potent inhibition of β-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM). Conclusions Synthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated.

Background Discovery of potent inhibitors of urease (jack bean) enzyme is the first step in the development of drugs against diseases caused by ureolytic enzyme. Results Thirty-two derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts were synthesized. All synthesized compounds (4a–z and 5a–s) were screened for their in vitro inhibition potential against urease enzyme (jack bean urease). The compounds 4i (IC50 = 17.6 ± 0.23 µM) and 5l (IC50 = 17.2 ± 0.44 µM) were found to be the most active members of the series, and showed several fold more urease inhibition activity than the standard compound thiourea (IC50 = 21.2 ± 1.3 µM). Whereas, compounds 4a–b, 4d–e, 4g–h, 4j–4r, 4x, 4z, 5b, 5e, 5k, 5n–5q having IC50 values in the range of 22.7 ± 0.20 µM–43.8 ± 0.33 µM, were also found as potent urease inhibitors. Furthermore, Molecular Dynamics simulation and molecular docking studies were carried out to analyze the binding mode of barbituric acid derivatives using MOE. During MD simulation enol form is found to be more stable over its keto form due to their coordination with catalytic Nickel ion of Urease. Additionally, structural–activity relationship using automated docking method was applied where the compounds with high biological activity are deeply buried within the binding pocket of urease. As multiple hydrophilic crucial interactions with Ala169, KCX219, Asp362 and Ala366 stabilize the compound within the binding site, thus contributing greater activity. Conclusions This research study is useful for the discovery of economically, efficient viable new drug against infectious diseases.Graphical abstract:STD. Thiourea (IC50 = 21.2 ± 1.3 µM) Electronic supplementary material The online version of this article (doi:10.1186/s13065-015-0140-1) contains supplementary material, which is available to authorized users.

Background Chalcones (1,3-diaryl-2-propen-1-ones, represent an important subgroup of the polyphenolic family, which have shown a wide spectrum of medical and industrial application. Due to their redundancy in plants and ease of preparation, this category of molecules has inspired considerable attention for potential therapeutic uses. They are also effective in vivo as anti-tumor promoting, cell proliferating inhibitors and chemo preventing agents. Results Synthesis and molecular structure investigation of (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one (3) is reported. The structure of the title compound 3 is confirmed by X-ray crystallography. The optimized molecular structure of the studied compound is calculated using DFT B3LYP/6-311G (d,p) method. The calculated geometric parameters are in good agreement with the experimental data obtained from our reported X-ay structure. The calculated IR fundamental bands were assigned and compared with the experimental data. The electronic spectra of the studied compound have been calculated using the time dependant density functional theory (TD-DFT). The longest wavelength band is due to H → L (79 %) electronic transition which belongs to π-π* excitation. The 1H- and 13C-NMR chemical shifts were calculated using gauge independent atomic orbitals (GIAO) method, which showed good correlations with the experimental data (R2 = 0.9911–0.9965). The natural bond orbital (NBO) calculations were performed to predict the natural atomic charges at different atomic sites. The molecular electrostatic potential (MEP) was used to visualize the charge distribution on the molecule. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound. Conclusions (E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one single crystal is grown and characterized by single crystal X-ray diffraction, FT-IR, UV–vis, DFT and optimized geometrical parameters are close to the experimental bond lengths and angles. Molecular stability was successfully analyzed using NBO and electron delocalization is confirmed by MEP. Prediction of Activity Spectra Analysis of the title compound, predicts anti-diabetic activity with probability to have an active value of 0.348. Graphical Abstract (E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one: a crystal structure and computational studies. Electronic supplementary material The online version of this article (doi:10.1186/s13065-015-0112-5) contains supplementary material, which is available to authorized users.