Mahendra Nath

An eco-friendly synthesis and antimicrobial activities of dihydro-2H-benzo- and naphtho-1,3-oxazine derivatives

A series of 3,4-dihydro-2H-benzo[e]-, 2,3-dihydro-1H-naphtho[1,2-e]-, 3,4-dihydro-2H-naphtho[2,1-e][1,3]oxazine and 1,2-bis(3,4-dihydrobenzo[e][1,3]oxazin-3(4H)-yl)ethane derivatives was obtained through an eco-friendly Mannich type condensation-cyclization reaction of phenols or naphthols with formaldehyde and primary amines in water at ambient temperature. Preliminary in vitro antimicrobial activity of the synthesized compounds was assessed against six pathogenic fungi, two Gram-negative and two Gram-positive bacteria. Some of the screened compounds have shown significant in vitro antimicrobial effect. Cytotoxic activities of the lead compounds (2m, 2n, 3c and 3d) against mouse fibroblast cell line (L929) were determined by MTT method. The assay results revealed that these molecules offered remarkable viability (>90%) of L929 cells at concentration of 25 microg/mL.

Recent approaches to antifungal therapy for invasive mycoses.

Antimycotic agents: Diverse classes of antimycotic drugs have been developed over the past decades with the goal of improving selectivity and efficacy. This review discusses both conventional and novel targets for antifungal agents and the possibility of vaccination in the treatment of invasive fungal infections.

Accelerated Bergman cyclization of porphyrinic-enediynesElectronic supplementary information (ESI) available: syntheses, characterization of 2a–4b, crystallographic files (CCDC 200680–200685) in CIF format. See http://www.rsc.org/suppdata/cc/b2/b212923j/

The Bergman cyclization of simple diethynylporphyrinic-enediynes exhibits a double activation barrier to the formation of Bergman cyclized product. Addition of H-atom acceptor accelerates the formation of the picenoporphyrin, indicating that the second barrier is rate limiting.

An eco-friendly Pictet–Spengler approach to pyrrolo- and indolo[1,2-a]quinoxalines using p-dodecylbenzenesulfonic acid as an efficient Brønsted acid catalyst

A facile and environmentally benign Pictet–Spengler strategy for the synthesis of a series of biologically important pyrrolo- and indolo[1,2-a]quinoxalines has been developed by reacting 1-(2-aminophenyl)-pyrrole or 1-(2-aminophenyl)indoles with a wide range of aromatic aldehydes, acetophenones or isatins in ethanol at ambient temperature using p-dodecylbenzenesulfonic acid (p-DBSA) as an efficient Bronsted acid–surfactant combined catalyst. This methodology was found to be applicable to generate diverse quinoxaline derivatives in fairly good yields under mild reaction conditions.

DBSA catalyzed, one-pot three-component “on water” green protocol for the synthesis of 2,3-disubstituted 4-thiazolidinones

A simple and environmentally benign one-pot three-component tandem synthesis of a series of novel 4-thiazolidinones has been accomplished “on water” by reacting aliphatic or aromatic primary amines with thioglycolic acid and a wide range of aromatic aldehydes at ambient temperature using p-dodecylbenzenesulfonic acid (DBSA) as a Bronsted acid-surfactant combined catalyst. The unique ability of the catalyst has been utilised to form emulsion droplets with organic substrates in aqueous medium whose interior core is hydrophobic enough to exclude the water molecules generated during the rate limiting dehydration step of the reaction. This protocol worked well with a variety of substrates and the desired products were obtained in fairly good yields.

Characterization of 7-amino-4-methylcoumarin as an effective antitubercular agent: structure–activity relationships

OBJECTIVES The objective of the present study was to evaluate the antitubercular activity of amino and acyl amino derivatives of coumarins when used alone and in combination with isoniazid, rifampicin, streptomycin or ethambutol, and to decipher the mode of action of the most effective agent. METHODS A series of amino and acyl amino coumarins were synthesized and screened for activity against the Mycobacterium tuberculosis H37Rv strain. These compounds were further evaluated by standard assay procedures to determine their MBCs, fractional inhibitory concentration index values and cytotoxicities. The MICs for a susceptible and a multidrug-resistant clinical isolate of M. tuberculosis were also determined. Electron and fluorescence microscopy of the test compound-treated mycobacterial samples were also carried out in an attempt to find out the target of action. RESULTS 7-Amino-4-methylcoumarin (7-amino-4-methyl-2H-chromen-2-one; NA5) displayed the lowest MIC of 1 mg/L against not only H37Rv but also the susceptible as well as the multidrug-resistant clinical isolates. Certain acyl amino coumarins were also found to inhibit the aforementioned strains and isolates with MICs in the range of 1.0-3.5 mg/L. They were also found to act in synergy with isoniazid/rifampicin. Electron microscopy revealed the cell-wall-attacking characteristic of these compounds, while fluorescence microscopy indicated that mycolic acid might be the target of action. CONCLUSIONS The present study clearly demonstrated the in vitro antitubercular potential of the novel drug candidate NA5. Further studies are warranted to establish the in vivo efficacy and therapeutic potential of NA5.

YFa, a Chimeric Opioid Peptide, Induces Kappa-Specific Antinociception with No Tolerance Development during 6 Days of Chronic Treatment

Our previous study showed that YGGFMKKKFMRFamide (YFa), a chimeric peptide of Met‐enkephalin, and Phe‐Met‐Arg‐Phe‐NH2 induced naloxone‐reversible antinociception and attenuated the development of tolerance to morphine analgesia. In continuation, the present study investigated which specific opioid receptors—μ, δ or κ—mediate the observed YFa antinociception pharmacologically using specific antagonists and whether chronic administration of YFa at 26.01 μmol/kg per day induces tolerance and its effect on the expression of μ and κ opioid receptors from day 4 to day 6, with endomorphine‐1 (EM‐1) and saline taken as positive and negative controls, respectively. Quantitative differential expression analysis was carried out by real‐time reverse‐transcriptase polymerase chain reaction, and the corresponding changes in protein levels were assessed by Western blot. A pharmacological investigation revealed that nor‐binaltorphimine, a specific κ opioid receptor–1 (KOR1) antagonist, completely antagonized the antinociception induced by 39.01 μmol/kg of YFa. Importantly, its chronic intraperitoneal administration did not result in significant tolerance over 6 days, whereas EM‐1 induced significant tolerance after day 4. Differential expression analysis revealed that EM‐1 caused up‐regulation of μ opioid receptor–1 on day 4, followed by down‐regulation on later days. Interestingly, YFa treatment caused a decrease on day 4, followed by an increase in the expression of KOR1 from day 5 onward. In conclusion, YFa induces kappa‐specific antinociception, with no development of tolerance during 6 days of chronic treatment, which further articulates new directions for improved designing of peptide‐based analgesics that may be devoid of adverse effects like tolerance.

An Expeditious Synthesis of Heteroarenes through Carbanion‐Induced Ring Transformation Reactions of Suitable Functionalized Pyran‐2‐ones

Pyrazolo[1,5-a]pyridines (3) and pyrano[4,3-d]pyrazolo[1,5-a]pyridines (4) have been synthesized from the reaction of pyran-2-one (1) and 5-aryl-3-cyanomethyl-1H-pyrazole (2) through carbanion-induced ring transformation reactions. A regioselective synthesis of highly functionalized polysubstituted pyrazolo[1,5-a]pyridines (6, 7) has also been achieved from the reaction of 2 with polarised ketene dithioacetals (5) and arylidenemalononitrile, respectively. An analogous reaction of 1 with 2-cyanomethyl-1H-benzimidazole (8) has also afforded the fused heterocycles 9 and 10. The cyano function in 9 has been exploited for acid-catalysed cyclization with thiosemicarbazide to obtain 11 in high yield.

Synthesis of sulphur heterocycles as hepatoprotectants : part I

Abstract The synthesis and hepatoprotective activity of 1,3-dithiolanes(2), 1,3-dithianes(3), 2H-thiopyran-2-thione(4), 1,3-dithiole-2-thione(5) and pyrazole(6) are described.

PEG–SO3H catalyzed, environmentally benign synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes under solvent-free conditions

A highly efficient, eco-friendly and high yielding procedure for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes has been developed through one-pot condensation reaction of β-naphthol with various aromatic aldehydes in the presence of a catalytic amount of sulfonated polyethylene glycol 6000 (PEG–SO3H) as a stable, recyclable and bio-degradable polymeric catalyst under solvent-free conditions. This protocol was found to be applicable to obtain a diverse range of dibenzoxanthene derivatives in 82–98% isolated yields and the catalyst was recycled for four cycles.