Golla Madhava

Synthesis, spectral characterization and bioactivity evaluation of novel α-aminophosphonates

GRAPHICAL ABSTRACT ABSTRACT A facile synthesis of novel α-aminophosphonates 5a-j was accomplished by condensation of imines (3a-j) with diethyl phosphite (4) in ethanol at 50–60°C using easily recoverable and reusable catalyst, tetramethyl guanidine (TMG) via pudovik reaction in high yields. All the title compounds were characterized by spectral and elemental analysis. They were further screened for their abilities towards in vitro antibacterial, antifungal and antioxidant activities. The compounds 5g, 5d, 5f exhibited good antibacterial and antifungal activities compared to the standard bactericide, Penicillin and fungicide, Griseofulvin, respectively. The compounds 5h, 5i, 5g, and 5c exhibited good antioxidant activity compared to the standard ascorbic acid.

Ultrasound-Promoted Synthesis of Biologically Active α-Hydroxyphosphonates/ Hydroxyphosphinates Using 1,4-Dimethylpiperazine as a Catalyst

Abstract A series of new α-hydroxyphosphonates/phosphinates was prepared using 1,4-dimethylpiperazine as a base catalyst under conventional as well as ultrasonic irradiation conditions by the reaction of 5-bromoindole-3-carboxaldehyde/2-nitrocinnamaldehyde with various phosphonates/phosphinates. The high yields of α-hydroxyphosphonates/hydroxyphosphinates were obtained in less reaction time under the ultrasonic irradiation method as compared with the conventional method. The synthesized compounds were screened for their in vitro and in vivo antioxidant activities, and the bio-screening data revealed that all the tested compounds exhibited good antioxidant activities. The bio-screening data revealed that compound 8e exhibited potent antioxidant activity in both in vitro and in vivo studies while the other compounds exhibited good antioxidant activity. [Supplementary materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, tables and figures.] GRAPHICAL ABSTRACT

N-Phosphorylated Derivatives of 5-Nitroindazole as Antimicrobial and Antioxidant Agents and Docking Study Against DNA Gyrasea

GRAPHICAL ABSTRACT Abstract A series of new phosphoramidate derivatives 7a-l were synthesized by reacting 5-nitroindazole with 4-chlorophenyl dichlorophosphate (4), and then further with various bio-potent aromatic/hetero/alkyl amines 6a-l. All the newly synthesized compounds were characterized by spectroscopic data (IR, 1H, 13C, 31P NMR and mass) and elemental analysis. The products 7a-l were evaluated for their antioxidant activity (DPPH, H2O2 methods and IC50 values) and antimicrobial activity against the growth of Gram bacterial (positive and negative) and fungal pathogens. In the entire bio-screening data, we observed that 7j is the most active compound in terms of its antimicrobial and antioxidant activities. Further to know the binding interactions of title products with DNA GyraseA enzyme (E. coli), molecular docking studies were performed which revealed 7j and 7k exhibited high binding affinities towards the enzyme, DNA GyraseA (GyrA), and are higher than that of the standard antibiotic, streptomycin.

Aryl/heteroaryl Substituted Celecoxib Derivatives as COX-2 Inhibitors: Synthesis, Anti-inflammatory Activity and Molecular Docking Studies

BACKGROUND Cyclooxygenase (COX-2) inhibitors have been developed to provide better anti-inflammatory and analgesic efficacy than those of traditional NSAIDs. Several compounds having selective COX-2 inhibitors such as SC-558, Celecoxib, Rofecoxib, Valdecoxib and Etoricoxib are marketed as new generation NSAIDs and block the production of prostaglandins (PGs) in inflammatory cells. New anti-inflammatory agents with improved potency and safety profile are still needed. OBJECTIVE As a part of our continuation research work towards new anti-inflammatory agents, the synthesis of N-substituted aryl/heteroaryl-pyrazole-1yl benzene sulfonamide (Celecoxib) derivatives, their anti-inflammatory activity in both methods in vitro and in vivo and molecular docking study on COX-2 enzyme will be discussed in this study. METHODS A series of N-substituted (aryl/heteroarylpyrazol-1-yl)benzenesulfonamide (Celecoxib) derivatives was synthesized and characterized them using IR, NMR (1H and 13C), mass and elemental analyses. Anti-inflammatory activity of the title compounds was evaluated by in vitro initially using albumin denaturation and membrane stabilization methods, enzymatic activity against COX-2 enzyme using colorimetric assay and then in vivo by carrageenan induced paw oedema and cotton pellet induced granuloma methods. The docking study was performed, to find the binding mode of the title compounds with the binding site of the COX-2 enzyme. RESULTS The biological activity screening data disclosed that some of the compounds 5b, 5e, 5f and 5i exhibited potent anti-inflammatory activity in both methods, in vitro and in vivo. The enzymatic assay on COX-2 enzyme demonstrated that few compounds potently inhibit COX-2 enzyme activity with IC50 of <0.89 μM. Unexpectedly, compound 5e (IC50, 0.62±0.17 μM) showed more potent COX-2 inhibited activity than that of parent drug, celecoxib (IC50, 0.62±0.25 μM) and the standard, flufenamic acid (IC50, 0.71±0.12 μM). CONCLUSION The bio-screening data, in vitro and in vivo anti-inflammatory activity and COX-2 enzymatic assay revealed that few N-substituteed aryl/heteroaryl-pyrazol-1-yl) benzene sulfonamides showed potent activity and compound 5e showed more potent COX-2 inhibit activity than that of parent drug, celecoxib and the standard, flufenamic acid. Moreover, all the newly synthesized title products were bonded well with good binding energies in the sight of COX-2 enzyme. Therefore, the described study might provide sustained information to the development of new series of derivatives with potent drug like activity.

CeCl3.7H2O-SiO2 Catalyzed Ultrasonicated Solvent-Free Synthesis of Carbamoyl/Carbamothioyl Phosphonates and Antimicrobial Activity Evaluation

GRAPHICAL ABSTRACT Abstract an expeditious and green method has been developed for the synthesis of a series of P‒C bond derivatives, diethyl substituted phenylcarbamoylphosphonates 6(a–e)/phenylcarbamothioylphosphonates 7(a–f) in high yields via simple addition reaction of isocyanates/isothiocyanates with diethyl phosphite in the presence of silica supported Lewis acid catalyst, SiO2-CeCl3.7H2O under solvent-free and sonication conditions. The advantages of this method are high yields, avoiding of harmful solvents, operational simplicity, shorter reaction time, and recoverability and recyclability of the catalyst. Antimicrobial activity was assayed for the title compounds, whereas the compounds 6c, 7b, and 7e against bacteria, and 6a, 7b, 7c, and 7e against fungi exhibited potential growth of inhibition.

Bismuth(III) Chloride Mediated Michaelis–Arbuzov Reaction: A Facile Synthesis of Substituted Arylphosphonates/Phosphinates and Bioactivity Evaluation

GRAPHICAL ABSTRACT Abstract BiCl3 is economically affordable, less toxic and eco-friendly catalyst. A facile synthesis of substituted arylphosphonates/phosphinates in good yields was achieved using BiCl3 catalyzed via Michaelis-Arbuzov reaction. 5-Iodovanillin/3,5-difluorobenzylbromide was reacted with various phosphites and dimethyl phenylphosphonite in the presence of Lewis acid catalyst BiCl3, under N2 atmosphere at 40°C to produce the corresponding arylphosphonates/phosphinates. They were characterized by 31P, 1H, and 13C NMR spectroscopy, IR, mass spectrometry, and elemental analysis. All title compounds were screened for their in vitro antibacterial and antifungal activity. The compounds 5d, 3b, 5e, and 5b exhibited good antibacterial activity and the compounds 3a, 3b, 5a, and 5d exhibited significant antifungal activity compared to the standard bactericide Norfloxacin and fungicide Griseofulvin.

Synthesis, spectral characterization, and pro- and antioxidant activity of phosphorylated derivatives of cis-tramadol

GRAPHICAL ABSTRACT ABSTRACT A series of new N-phosphorylated derivatives of cis-tramadol were synthesized in a two-step process with good yields to evaluate the pro- and antioxidant activities (LPO, NO2−, total SOD, and CAT). In the first step, cis-tramadol (1) was treated with 4-nitro/2-chlorophenyl phosphorodichloridate (2/3) in the presence of triethylamine (TEA) to yield the intermediates (4/5). Further these were subsequently treated with various primary and secondary amines in the presence of TEA to afford (1R)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexyl substituted phosphonates/phosphoramidates (6a-f/7a-f). Their structures were established by IR, NMR (1H, 13C, 31P), mass spectra, and C, H, N analysis. From the results it was disclosed that phosphonate derivatives (6a-f) exhibited more potent antioxidant activity than that of phosphoramidate derivatives (7a-f).

Synthesis Of New P-substituted Iminophosphoranes Via Staudinger Raction And Antimicrobial Activity Evaluation

GRAPHICAL ABSTRACT Abstract A class of two series of new P-substituted iminophosphoranes, N-(1,3-benzothiazol-2-ylmethyl)-N-(alkyl subtituted-λ5-phosphanylidene)amine 5(a-e) and N-(alkyl substituted-λ5-phosphanylidene)-(3,5-difluorophenyl)methanamine 9(a-e) was accomplished via Staudinger reaction of sodium azide, 2-chloromethyl benzothiazole (1) or 3,5-difluorobenzylbromide (6) and various trivalent alkyl/aryl phosphines/ethyldiphenylphosphinite/dimethylphenylphosphonite 4(a-e). The structures of new products were elucidated from spectroscopic data and elemental analysis. In vitro antibacterial and antifungal activities of the title compounds were investigated against four bacterial strains and three fungal strains at 50 and 100 μg/mL concentrations, respectively. The minimum inhibitory concentration (MIC) of the title compounds were also determined. Among all the compounds, 3,5-difluorobenzyl core derivatives 9a and 9b, and 1,3-benzothiazol-2-ylmethyl constituent containing compounds, 5b and 5c showed promising antibacterial and antifungal activities, respectively, at lower MIC values in the range of 6.25–25.0 μg/mL and approximately closer to the standards.

Synthesis of Novel N,N-Disubstituted Ethyl P-[2-(1H-Indol-3-YL)Acetyl]Phosphoramidates and Their Biological Activity

GRAPHICAL ABSTRACT Abstract A series of novel N,N-disubstituted ethyl P-[2-(1H-indol-3-yl)acetyl]phosphoramid-ates were synthesized. All title compounds were characterized by IR, NMR (1H, 13C, 31P) spectra, mass spectra, and C, H, N analysis. The anticancer activity of the title compounds was evaluated in two human cell lines MCF-7 (breast cancer) and HeLa (Cervical cancer) cell lines by the use of the MTT assay, and the IC50 values were determined. The derivatives with substituted piperazines exhibited significant cytotoxicity against the tested cell lines at 5 μM and displayed low IC50 values in the region of 5.8–8.8 μM for MCF-7 cell lines and 14.8–16.4 μM for HeLa cell lines when compared with the standard doxorubicin (5.4 and 14.2 μM).