A facile and metal-free domino reaction of TsDAM and 2-alkenylarylaldehyde: An easy access to 8-hydroxy-2,8-dihydro indeno [2,1-]pyrazoles.

An efficient straightforward metal free domino approach was developed for the synthesis of various 8-hydroxy-2,8-dihydroindeno[2,1-c]pyrazoles via [3 + 2] cycloaddition of substituted alkenes and TsDAM (TosylDiAzoMethane). The salient features of this protocol include high efficiency, mild reaction conditions, greener solvent, metal-free reaction, scalability and broad substrate scope along with high regioselectivity and yields.

Regioselective Ring Expansion of 3-Ylideneoxindoles with Tosyldiazomethane (TsDAM): A Metal-Free and Greener Approach for the Synthesis of Pyrazolo-[1,5-]quinazolines.

An efficient, metal-free approach to access pyrazolo-[1,5-]quinazolines with 3-ylideneoxindoles and tosyldiazomethane (TsDAM) under mild aqueous reaction conditions has been developed and the solvent involvement in the present reaction has also been explored for the first time. This greener approach involves 1,3-dipolar cycloaddition, regioselective ring expansion, followed by the elimination of tosyl group with aqueous base in a single operation, and the product can be isolated in high purity without column chromatographic separation. The method is also compatible with a large variety of functional groups, providing good to excellent yields in water, thus resulting in a decrease of environmental impact in the pharmaceutical industry.

Regioselective ring expansion followed by H-shift of 3-ylidene oxindoles: a convenient synthesis of N-substituted/un-substituted pyrrolo[2,3-] quinolines and marinoquinolines.

Herein, we report a simple and metal-free protocol for the synthesis of 4-oxo-4,5-dihydro-3-pyrrolo[2,3-]quinolines. The present method under mild reaction conditions with wide functional group compatibility gives several unexplored N-substituted/unsubstituted 4-oxo-4,5-dihydro-3-pyrrolo[2,3-]quinolines and marinoquinolines in good to excellent yields. Mechanistic insights for the synthesis of N-substituted pyrroloquinolines reveal the ring expansion of 3-ylideneoxindoles and H-shift as the key steps.

Solvent-Controlled, Tunable Domino Reaction of 3-Ylideneoxindoles with in Situ-Generated α-Aryldiazomethanes: A Facile Access to 3-Spirocyclopropyl-2-oxindole and Pyrazoloquinazolinone Scaffolds.

A mild and efficient solvent-controlled, metal-free switchable 1,3-dipolar cycloaddition/ring contraction or ring expansion domino reaction of 3-ylideneoxindoles with in situ-generated α-aryldiazomethanes has been developed. This domino reaction provided a series of aryl-substituted 3-spirocyclopropyl-2-oxindoles and pyrazoloquinazolinones with excellent regio- and diastereoselectivity from common substrates under varying solvent conditions.

Design, synthesis, and antimicrobial evaluation of 1,4-dihydroindeno[1,2-]pyrazole tethered carbohydrazide hybrids: exploring their ADMET, ergosterol inhibition and ROS inducing potential.

A series of new 1,4-dihydroindeno[1,2-]pyrazole tethered carbohydrazide hybrids () were designed, synthesized and evaluated for their antimicrobial activity. Compounds , , , and demonstrated significant activity against the entire panel of test pathogens. Further, compounds and exhibited significant anti- activity.

Antioxidant Studies on Ethanol Extracts from Two Selected Genera of Indian Lamiaceae.

The present work is targeted to evaluate antioxidant activity of ethanol extracts from the leaves of Plectranthus mollis and Salvia officinalis belonging to family Lamiaceae using nitric oxide scavenging, hydrogen peroxide scavenging, ferric reducing antioxidant power assay and lipid peroxidation methods. The results of the study indicate that the leaf extracts of both the plants possess in vitro antioxidant activity. The higher amount of flavanoids and phenolic compounds may correspond to their greater antioxidant activity.

Neural pathology in leprosy during treatment and surveillance.

The histological findings of 22 patients with neuritis, 14 developing pain, tenderness and swelling during treatment and 8 during surveillance are presented in this study. Seven patients' biopsies showed macrophage type and 14 had epithelioid cell type of granulomas. All biopsies showed evidence of active disease, except for two patients with macrophage granulomas where some regressive changes were evident.

Reactions in borderline leprosy.

This is a retrospective study of 276 patients consisting of 157 active and 119 reactive patients of borderline leprosy. They were followed up for 10 years after sulphone monotherapy. The presenting symptoms were carefully examined from the records and systematically presented.

Chromosomal aberration, micronucleus and Comet assays on peripheral blood lymphocytes of leprosy patients undergoing multidrug treatment.

To evaluate the genetic damage in leprosy patients, we carried out the alkaline Comet assay and chromosomal aberration (CA) and micronucleus (MN) tests in peripheral blood lymphocytes of 50 leprosy patients receiving multidrug treatment (MDT) and 50 healthy individuals. The Comet assay showed statistically higher mean values for length to width ratios of DNA mass (P < 0.01) and for mean frequencies of tailed cells (P < 0.

Correlation of clinical, histological and immunological features across the leprosy spectrum.

The Ridley-Jopling system of classification of the variegated clinical pattern of leprosy is based on the specific cell-mediated immunity observed in the histopathology of skin lesions conforming to a spectrum from TT at one end to LL at the other. In this study a fairly large sample of 90 patients was classified on clinical grounds; the histopathology of the skin lesions was studied blind. There was an overall concordance of 90% between the clinical and histological classifications.

Poor correlation of systemic immunological parameters with clinical features in macular leprosy.

On the basis of clinical features and bacteriological status, macular skin lesions of nine cases of leprosy were classified as falling within a spectrum between the tuberculoid at one end and the lepromatous at the other. While histologic correlation was seen in 60% of cases, humoral and cellular systemic immunologic features were found to be uncharacteristic. It is suggested that macular lesions form an early stage in the development of leprosy where the systemic immunological response is yet to set in fully.

Detection of disease related immune complexes in the serum of leprosy patients. A novel single step method.

Mycobacterium leprae antigen and antibody complexes could be detected in the serum of leprosy patients using monoclonal antibody ML34 and anti-BCG antibodies by enzyme-linked immunosorbent assay. This simplified system detects disease related complexes without the need for isolating and purifying them from the serum. Immune complexes captured using monoclonal antibody ML34 revealed positivity in seven out of eight neuritic, two out of nine tuberculoid (TT), five out of ten borderline tuberculoid (BT), four out of ten borderline lepromatous (BL) and four out of ten lepromatous (LL), leprosy cases.

A sequential study of circulating immune complexes, complement and immunoglobulins in borderline tuberculoid leprosy patients with and without reactions.

Sequential estimates of the levels of circulating immune complexes (CIC), complement catabolic fragment C3d, complement-mediated immune complex solubilization (CMS) and immunoglobulins were made in 24 newly diagnosed with borderline tuberculoid leprosy over a 20 month period after initiation of chemotherapy. Fourteen of these patients had not suffered from reversal reactions either at the time of presentation or during the follow-up. The levels of CIC were evaluated in them from the third to the eleventh month after starting chemotherapy and immunoglobulin G (IgG) levels were evaluated up to eight months.

Histological and immunological correlates of suspected leprosy lesions.

Thirty-two subjects with suspected leprosy lesions were investigated to assess various modalities of sensibility and sweat function and these were correlated with immunological and histological parameters. It was found that pain and temperature, mediated by small unmyelinated fibres were impaired in the early lesions. Impairment of sweat function was seen only when one of the modalities of sensibility was also affected.

Immunological profiles of leprosy patients and healthy family contacts toward M. leprae antigens.

In this study, we measured simultaneously the in vitro and in vivo T lymphocyte reactivities and the antibody responses of leprosy patients and healthy family contacts (HFC) toward Mycobacterium leprae antigens. The in vitro lymphoproliferative response of the HFC to leprosin A was comparable to that of tuberculoid leprosy patients. However, their skin-test reactivity to Dharmendra lepromin was considerably higher compared to the in vitro response to leprosin A.

Detection of antibodies against phenolic glycolipid-1 (PGL-1), 35-kDa and 30-40-kDa components of Mycobacterium leprae in the cerebrospinal fluid of of leprosy patients.

The involvement of the central nervous system (CNS) in lepromatous leprosy (LL) patients was investigated; 33 patients were examined clinically in detail and upper motor neuron involvement was observed in eight and lower motor neuron in three of these patients. Anti-Mycobacterium leprae antibodies could be detected in the CSF by PGL-1 enzyme-linked immunosorbent assay (ELISA) and monoclonal antibody (MAb) based competitive assays against defined epitopes on the 35-kDa protein and 30-40-kDa polysaccharide (lipoarabinomannan) antigens with MAbs MLO4 and ML34, respectively. Antibodies against PGL-1 and 35-kDa protein were observed in more subjects than antibodies against the 30-40-kDa antigen.

IgG subclass antibodies to mycobacterial sonicate and recombinant antigens in leprosy.

In this study the IgG subclass antibodies to sonicated preparations of Mycobacterium leprae (leprosin A) and BCG (BCG-S) as well as to purified recombinant 65 kDa protein of M. leprae (rML65) were analysed in sera from leprosy patients and healthy household contacts (HFC) and noncontacts (HNC) in a leprosy endemic population. In LBI+ (lepromatous bacterial index positive) patients, IgG3 was predominant in the responses to sonicated antigens of M.

Clinical features and diagnosis of relapses in leprosy.

1. The definition of relapse as "occurrence of new signs and symptoms of the disease during the period of surveillance or thereafter in a patient who successfully completes an adequate course of multidrug therapy" accommodates the current policy of releasing patients even when there are clinical and bacteriological signs of activity after fixed duration treatment. 2.

Critical residues of the Mycobacterium leprae LSR recombinant protein discriminate clinical activity in erythema nodosum leprosum reactions.

We reported earlier (S. Singh, N. P.