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1.
J Inorg Biochem ; 237: 111993, 2022 12.
Article in English | MEDLINE | ID: mdl-36108344

ABSTRACT

This work describes the synthesis, characterization and in vitro anticancer activity of two platinum(II) complexes of the type [Pt(L1)2(1,10-phen)] 1 and [Pt(L2)2(1,10-phen)] 2, where L1 = 5-heptyl-1,3,4-oxadiazole-2-(3H)-thione, L2 = 5-nonyl-1,3,4-oxadiazole-2-(3H)-thione and 1,10-phen = 1,10-phenanthroline. As to the structure of these complexes, the X-ray structural analysis of 1 indicates that the geometry around the platinum(II) ion is distorted square-planar, where two 5-alkyl-1,3,4-oxadiazol-2-thione derivatives coordinate a platinum(II) ion through the sulfur atom. A chelating bidentate phenanthroline molecule completes the coordination sphere. We tested these complexes in two breast cancer cell lines, namely, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both cells, the most lipophilic platinum compound, complex 2, was more active than cisplatin, one of the most widely used anticancer drugs nowadays. DNA binding studies indicated that such complexes are able to bind to ct-DNA with Kb values of 104 M-1. According to data from dichroism circular and fluorescence spectroscopy, these complexes appear to bind to the DNA in a non-intercalative, probably via minor groove. Molecular docking followed by semiempirical simulations indicated that these complexes showed favorable interactions with the minor groove of the double helix of ct-DNA in an A-T rich region. Thereafter, flow cytometry analysis showed that complex 2 induced apoptosis and necrosis in MCF-7 cells.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Humans , Phenanthrolines/pharmacology , Phenanthrolines/chemistry , Platinum/chemistry , Thiones , Molecular Docking Simulation , Antineoplastic Agents/chemistry , DNA/chemistry , Coordination Complexes/chemistry , Cell Line, Tumor
2.
J Org Chem ; 83(24): 15144-15154, 2018 12 21.
Article in English | MEDLINE | ID: mdl-30450907

ABSTRACT

The first report of the preparation of symmetric and nonsymmetric diaminotruxinic derivatives through the photoredox [2 + 2] cycloadditions of Erlenmeyer azlactones is described, affording the desired compounds in high regio- and diastereocontrol (only head-to-head coupling). Mechanistic studies by DFT suggest that the reaction proceeds through a neutral photocatalytic pathway.

3.
ACS Omega ; 2(6): 2967-2976, 2017 Jun 30.
Article in English | MEDLINE | ID: mdl-31457632

ABSTRACT

An organocatalytic protocol, employing the commercially available EDC as coupling agent, has been developed for the preparation of dual-protected amino acid derivatives without epimerization. This methodology was then applied to different Boc-amino acid and amine derivatives in moderate to excellent isolated yields. In addition, racemization-free Boc deprotection was also demonstrated. Mechanism investigation through electrospray ionization (+)-mass spectrometry/mass spectrometry revealed an acyclic intermediate (no azlactone formation) activated by the camphorsulfonic acid as an organocatalyst as a key step for the sequential attack of the nucleophile.

4.
Org Lett ; 17(5): 1248-51, 2015 Mar 06.
Article in English | MEDLINE | ID: mdl-25679260

ABSTRACT

A simple and mild method is demonstrated for assembling acyl carbamates through a base-free four-component Pd-catalyzed carbonylation of aryl halides in the presence of potassium cyanate and alcohols in a two-chamber system. This approach produces a wide range of aryl acyl carbamates in good to excellent yields from the corresponding aryl bromides or iodides with near-stoichiometric carbon monoxide. In addition, the method can be extended to the synthesis of primary amides thereby expanding the usefulness of cyanate as an ammonia equivalent.


Subject(s)
Alcohols/chemistry , Carbamates/chemical synthesis , Cyanates/chemistry , Hydrocarbons, Halogenated/chemistry , Palladium/chemistry , Amides/chemistry , Ammonia/chemistry , Carbamates/chemistry , Catalysis , Molecular Structure
5.
J Org Chem ; 80(3): 1920-8, 2015 Feb 06.
Article in English | MEDLINE | ID: mdl-25565181

ABSTRACT

A useful method was developed for the synthesis of active esters by palladium-catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS), pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N-hydroxyphthalimide. A high functional group tolerance was displayed, and several active esters were prepared with good to excellent isolated yields. The protocol was extended to access an important synthetic precursor to the HIV-protease inhibitor, saquinavir, by formation of an NHS ester followed by acyl substitution.


Subject(s)
Bromides/chemistry , HIV Protease Inhibitors/chemistry , HIV Protease Inhibitors/chemical synthesis , Hydrocarbons, Halogenated/chemistry , Palladium/chemistry , Phthalimides/chemistry , Saquinavir/chemistry , Saquinavir/chemical synthesis , Succinimides/chemistry , Catalysis , Esters , Molecular Structure
6.
Bioorg Med Chem Lett ; 24(19): 4626-4629, 2014 Oct 01.
Article in English | MEDLINE | ID: mdl-25219900

ABSTRACT

In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and for their antifungal activity against four species of Candida (C. albicans, C. tropicalis, C. glabrata and C. parapsilosis). Compounds 5a (N-(2-aminoethyl)dodecanamide), 5b (N-(2-aminoethyl)tetracanamide) and 6d (N-(3-aminopropyl)oleamide) were the most active against Gram-positive bacteria, with MIC values ranging from 1 to 16µg/mL and were evaluated for their activity against 21 clinical isolates of methicillin-resistant S. aureus. All the compounds exhibited good to moderate antifungal activity. Compared to chloramphenicol, compound 6b displayed a similar activity (MIC50=16µg/mL). A positive correlation could be established between lipophilicity and biological activity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Candida/drug effects , Diamines/pharmacology , Gram-Negative Bacteria/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Diamines/chemical synthesis , Diamines/chemistry , Dose-Response Relationship, Drug , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
7.
Bioorg Med Chem Lett ; 23(10): 2883-7, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23587426

ABSTRACT

We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis). The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds. The best activities were obtained against the Gram-positive bacteria (MIC=2-16µgml(-1)) for the five compounds bearing longer alkyl chains (4c-g; 8-14 carbons), which were also the most active against Candida (MIC=2-64µgml(-1)). Compound 4e exhibited the highest levels of inhibitory activity (MIC=2-16µgml(-1)) against clinical isolates of MRSA. A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates.


Subject(s)
Amino Alcohols/pharmacology , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Surface-Active Agents/pharmacology , Amino Alcohols/chemical synthesis , Amino Alcohols/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Dose-Response Relationship, Drug , Molecular Structure , Structure-Activity Relationship , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistry
8.
Chem Biol Drug Des ; 78(5): 876-80, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21883957

ABSTRACT

Two series of aromatic and heteroaromatic amino alcohols were synthesized from alcohols and aldehydes and evaluated for their antibacterial activities. All the octylated compounds displayed a better activity against the four bacteria tested when evaluated by the agar diffusion method and were selected for the evaluation of minimal inhibitory concentration. The best results were obtained for p-octyloxybenzyl derivatives against Staphylococcus epidermidis (minimal inhibitory concentrations = 32 µm).


Subject(s)
Amino Alcohols/chemistry , Amino Alcohols/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Amino Alcohols/chemical synthesis , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Staphylococcus epidermidis/drug effects , Structure-Activity Relationship
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