Novel amidase catalysed process for the synthesis of vorinostat drug.

AIM: Presently, N-hydroxy-N'-phenyloctanediamide (vorinostat) which is an effective histone deacetylase inhibitor, is being synthesized chemically. Hence, present study aims to develop an eco-friendly approach for the synthesis of vorinostat from N'-phenyloctanediamide through biotransformation. METHODS AND RESULTS: Using the amidase of Bacillus smithii IIIMB2907 in time course conversion and organic solvent compatibility, maximum bioconversion was observed at 12 h of reaction time and in presence of ethanol, respectively. Potassium phosphate buffer of pH 7·0 supported maximum bioconversion of N'-phenyloctanediamide (10 mmol l-1 ) into N-hydroxy-N'- phenyloctanediamide at 40°C. Bench scale study was successfully carried out with 83% yield of purified vorinostat. CONCLUSION: In this study, an eco-friendly approach for the biotransformation of N'-phenyloctanediamide into vorinostat was developed by using cell free extract of thermophilic strain B. smithii IIIMB2907. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial amidase has achieved remarkable attention in the field of biotransformation for the green synthesis of hydroxamic acids. Utilization of amidase from B. smithii IIIMB2907, specifically in the synthesis of vorinostat drug is a foremost attempt in the development a novel process and can also be employed in the synthesis of its derivatives as well.

Microwave-assisted synthesis, characterization and biological screening of nitrogen-sulphur and nitrogen-oxygen donor ligands and their organotin(IV) complexes.

Series of new trigonal bipyramidal and octahedral complexes of tin(IV) have been synthesized by the reaction of dimethyltin(IV) dichloride with 4-nitro-benzanilidethiosemicarbazone (L(1)H), 4-chlorobenzanilidethiosemicarbazone (L(2)H), 4-nitrobenzanilidesemicarbazone (L(3)H) and 4-chlorobenzanilidesemicarbazone (L(4)H). The unimolecular and bimolecular reactions of dimethyltin(IV) dichloride and monobasic bidentate ligands were carried out using microwave irradiations as the thermal energy source and the complexes so formed were characterized by elemental analysis, conductance measurements, molecular weight determinations and spectral data, viz. IR, UV-vis, (1)H and (13)C NMR. The complexes have also been prepared by the general thermal methods for comparison purposes. The comparison data support the synthesis using the microwave route, i.e. green chemistry route. The tin(IV) complexes show penta-coordinated structure for 1:1 complexes and hexa-coordinated for 1:2 complexes. The antifungal, antibacterial and antifertility activities have been examined and the results were indeed very encouraging.

Temporal expression of transforming growth factor-beta2 and myostatin mRNA during embryonic myogenesis in Indian broilers.

TGF-beta2 and myostatin, the members of TGF family, act through both autocrine and paracrine mechanisms to regulate the growth and differentiation at various developmental stages in chicken. The kinetics and expression profile of these two growth factors were investigated by semi-quantitative RT-PCR, during the myogenesis of Indian broiler chickens. Total RNA was isolated from whole embryos on each of embryonic days (E) 0-6 (n=3 per day) and from the biceps femoris muscle at E7-E18 (n=3 per day). The expression of TGF-beta2 was noticed on E2 that remained at the same level until E6. In biceps femoris muscle, higher level of TGF-beta2 expression was observed during E7-E12, which decreased gradually thereafter. These findings suggested that TGF-beta2 might be a regulatory factor participating in the myogenesis of chicken embryos. Initial myostatin expression was noticed on E1, even before the myogenic lineage is established in embryo. This finding suggested an additional role of myostatin in early chicken embryo development, other than myogenesis. Furthermore, myostatin expression was significantly higher on E3 as compared to earlier studies, where initial higher level was observed at E2, suggesting the differential expression of myostatin among breeds. Higher and almost static myostatin expression was noticed in biceps femoris muscle during the entire period of myogenesis (E7-E18). In the present study, the ontogeny of myostatin expression coincided with myogenesis of chicken. Therefore, it may be hypothesized that myostatin is not only a major determinant of muscle mass, but also involved in early embryogenesis in chickens.

Investigations of the possible pharmacological effects of organotin(II) complexes.

Antitumour, antifertility and histopathological investigations were carried out on male rats by the use of organotin complexes. The organotin complexes were synthesized by the alkylation of [Sn(TAML(n))Cl(2)] (n=1-4 and TAML(n) represents the tetraazamacrocyclic ligands) in the presence of CH(3)I or C(2)H(5)Br. The structures of all the complexes have been established on the basis of elemental analyses, conductivity measurements, IR, (1)H NMR, (13)C NMR, (119)Sn NMR and X-ray spectral data. The antitumour effect of the compounds was examined on swiss mice. The results obtained clearly indicated that the compounds, [C(2)H(5)Sn(TAML(3))C(5)H(5)N] and [C(2)H(5)Sn(TAML(4))C(5)H(5)N] display effective antitumour activity. The emphasis has been given on in vivo study on male albino rats (Rattus norvegicus) by performing serum analyses, blood analyses and fertility test.

The human glutathione S-transferases: comparison of isoenzyme expression in normal and astrocytoma brain.

We describe expression of alpha, mu and pi class glutathione S-transferases (GST) in brain tissue from 21 controls and uninfiltrated and tumour tissue from 17 glioma patients. GST were sequentially resolved by chromatofocusing into the GST2, GST1, GST5, GST2 (5.5), GST3, GST6 sets and the contribution of each to total activity determined. The immunological identity of these isoforms was studied using immunoblotting. The pi class GST3 isoform was the major contributor to activity in control tissue (70.9%) and, uninfiltrated (75.1%) and tumour samples (82.4%). Expression was significantly greater in the tumours (P less than 0.05). Expression of alpha isoforms GST2 and GST2 (5.5) was variable with most subjects demonstrating no detectable GST2 (B1 and B2 chromatofocused monomers). An isoform termed GST2 (5.5) chromatofocussed at pH 5.5 and cross-reacted with antisera to B1. It was detected in most control and glioma patients and comprised about 5% of total activity. The contribution of GST2 and GST2 (5.5) to activity was similar in control, uninfiltrated and tumour tissue. Two mu class enzymes, GST1 and GST5, were identified. GST1 isoforms were detected in 9 of 21 control samples, the phenotype of these and matched liver samples were identical. GST1 isoforms were detected in 4 of 16 tumour samples, a significantly lower incidence than in a previously established control group. GST5 was expressed in most samples, the contribution of this locus to activity was significantly reduced in the tumours (5.2%) compared with control samples (14.5%).

Differential expression of inducible nitric oxide synthase and cytokine mRNA in chicken lines divergent for cutaneous hypersensitivity response.

Phytohemagglutinin (PHA)-induced delayed-type hypersensitivity is an immunocompetent trait considered an indicator of cell-mediated immune or T-cell responses. Divergent selection was performed to generate high and low lines for response to PHA-P. Extreme-responder birds of the F2 generation in each line were used to study possible differences in macrophage activity and the associated functional genes. To evaluate macrophage activity, nitric oxide (NO) was estimated both systemically in serum and in in vitro monocyte culture. Semi-quantitative RT-PCR was used to detect the differential mRNA expression patterns of iNOS and MIP-1beta in monocyte culture, whereas T(H)1 cytokines (IL-2 and IFN-gamma) were studied in peripheral blood mononuclear cells (PBMC) at different time intervals after lipopolysaccharide (LPS) induction. The high line showed strong systemic, as well as in vitro NO production, compared to the low line, upon stimulation with NDV and LPS, similar to early and high iNOS mRNA expression. Following the pattern of iNOS gene expression, an early strong expression of cytokines with powerful iNOS-inducing action, such as IFN-gamma and the chemokine MIP-1beta, was observed in the high line. In contrast, for response to PHA-P, low expression of IL-2 was observed in the high compared to the low line. In conclusion, the study revealed that divergent selection for response to PHA-P resulted in a divergent effect on T(H)1 cell activity, resulting in altered macrophage function in chickens. Selection, based on response to PHA-P, could lead to more resistant birds or birds with an enhanced immune response.

Uranium series disequilibrium studies in Chenchu colony area, Guntur district, Andhra Pradesh, India.

An attempt is made to understand uranium series disequilibrium in unconformity proximal related uranium mineralisation in Chenchu colony area, Guntur district, Andhra Pradesh, India. The uranium mineralization in Chenchu colony is the western continuity of the Koppunuru uranium deposit and predominantly hosted by gritty quartzite/conglomerate, which occasionally transgresses to underlying basement granite/basic rock. Disequilibrium studies are based on borehole core samples (35 boreholes, No. of samples=634) broadly divided in two groups of cover rocks of Banganapalle formation (above unconformity) and basement granites (below unconformity). Linear regression coefficient between uranium and radium is 0.95, which reflects excellent correlation and significant enrichment of parent uranium. Disequilibrium studies have indicated predominant disequilibrium in favour of parent uranium (35%), which is probably due to the weathering process causing migration of some of the radionuclides while dissolution of minerals due to groundwater action might have also played a significant role. Further, escape of radon might have accentuated the disequilibrium factor resulting in an increase in the grade of the mineralization. This is well corroborated by the presence of fractures and faults in the study area providing channels for radon migration/escape.

Biologically relevant tetraazamacrocyclic complexes of manganese: synthetic, spectral, antimicrobial, antifertility and antiinflammatory approach.

The testicular sperm density, sperm morphology, sperm motility, density of cauda epididymis spermatozoa and fertility in mating trials and biochemical parameters of reproductive organs have been examined and discussed for [Mn(N(4)MacL(n))(NO(3))(2)] (where N(4)MacL(n) represents the tetraazamacrocyclic ligand molecule with n=1-4) type of complexes. An attempt also has been made to correlate the structural aspects of the compounds with their anti-inflammatory activity. The 14-18 membered tetraamide macrocyclic ligands N(4)L(1)-N(4)L(4) used during these investigations have been prepared by the condensation of 1,2-diaminoethane or 1,3-diaminopropane with malonic or succinic acid in the presence of condensing reagents, dicyclohexylcarbodiimide and 4-dimethylaminopyridine. On reduction, these macrocyclic ligands give a new series of tetraazamacrocyles [N(4)MacL(n)] and their complexes with manganese(II) nitrate. The ligands and their complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, mass and X-ray structural analyses. An octahedral geometry for these complexes has been confirmed by spectral studies. On the basis of the chemical composition, the representation of the complexes as [Mn(N(4)MacL(n))(NO(3))(2)] has been established. The ligands and their complexes have been screened in vitro against a number of pathogenic fungi and bacteria to assess their growth inhibiting potential.

Unsymmetrical borole complexes as biocides: synthetic, structural and biological aspects.

Triisopropoxyborane on treatment with catechol in equimolar ratio in excess of benzene affords the formation of 2-isopropoxybenzo-1,3-dioxa-2-borole [OC6H4OB(OPri)]. The interaction of [OC6H4OB(OPri)] with benzothiazolines, prepared by the condensation of [1-(2-thienyl)ethanone], [1-(2-pyridinyl)ethanone], [1-(2-furanyl)ethanone], and [1-(2-naphthenyl)ethanone] with 2-mercaptoaniline, yields complexes that have B--O, B--S, and B<--N bonds. The unsymmetrical borole complexes were subjected to microestimations and spectral analyses comprised of UV, IR, proton-1, boron-11, and carbon-13 nuclear magnetic resonance studies. The spectral studies point to a tetracoordinated environment around boron because the stereochemically active lone pair is also included in the coordination sphere. X-ray powder diffraction of a representative complex also has been carried out. In the quest for better fungicides and bactericides, studies were conducted to assess the growth-inhibiting potential of the synthesized complexes along with the ligands against various fungal and bacterial strains. The studies demonstrate that the concentrations reach levels that are sufficient to inhibit and kill the pathogens. Furthermore, the results achieved from biological activity also have been compared with the conventional fungicide, Bavistin, and conventional bactericide, Streptomycin.

Triorganosilicon (IV) compounds: synthesis, structural study, and biological activity.

A few coordination compounds of silicon (IV) have been synthesized by the interaction of trimethyl- and triphenyl-chlorosilane with nitrogen-sulphur donor ligands. These compounds are monomeric, as indicated by molecular weight determination, and they behave as nonelectrolytes in dry DMF. From the electronic, infrared, 1H, and 13C NMR spectral results, it has been concluded that in these compounds, silicon is penta-coordinated in a trigonal bipyramidal environment. An assessment of biological activity of these compounds has shown that some of them are very active against P. mirabilis and others against S. viridans bacteria, while all of them show good fungicidal action against F. oxysporum, A. alternata, and A. niger.

Stereochemical and biochemical aspects of some organoboron complexes of sulphur donor ligands.

Synthetic, structural and biochemical aspects of some organoboron complexes of sulphur containing ligands having ONS and SNNS donor systems have been described. The ligands were prepared by the condensation of 1-phenyl-1,3-butanedione, 2,4-pentanedione, diphenylethanedione, 2,3-butanedione, ethanedial and 1,4-benzenedialdehyde with 2-mercaptoaniline. The unimolar reactions between phenylboronic acid and these thio-ligands have produced Ph.B (ONS) and Ph.B. (SNNS) type of biologically active complexes. These have been characterized by elemental analysis, molecular weight determinations, and conductivity measurements. Based on UV, IR, 1H NMR, 13C NMR and 11B NMR spectral studies, a tetracoordinated state of boron has been established in all the derivatives. The ligands and their corresponding organoboron complexes have been tested in vitro against a number of pathogenic fungi and bacteria and found to possess remarkable fungicidal and bactericidal properties.

Coordination behavior and antifungicidal, antibacterial, and antifertility activities of dioxomolybdenum(VI) complexes of biologically active heterocyclic benzothiazolines.

Synthesis, characterization, and structural aspects of a new class of dioxomolybdenum(VI) complexes with biologically active benzothiazolines, 2-(2-pyridyl) benzothiazoline, 2-(2-thienyl) benzothiazoline, 2-(2-furyl) benzothiazoline, 2-(3-indolyl) benzothiazoline, glyoxal benzothiazoline, biacetylbenzothiazoline, benzil benzothiazoline, and terphthaldehyde benzothiazoline have been described. The newly synthesized complexes, [MoO2(Bzt)2] and [MoO2(Bzt')] (where BztH and Bzt'H2 represent benzothazoline molecules) have been characterized by elemental analysis, conductance measurements, molecular weight determinations, and magnetic studies. Based on IR, 1H NMR, 13C NMR, and electronic spectral studies, distorted octahedral geometry with cis-MoO2 group has been indicated for the resulting complexes. Two benzothiazolines and their corresponding metal complexes were screened for their antifungicidal and antibacterial activity on several fungi and bacteria and found to be quite active in this respect. In addition, antifertility activity of representative ligands and their molybdenum complexes was also evaluated and discussed in male mice.

Antifertility, antibacterial, antifungal and percent disease incidence aspects of macrocyclic complexes of manganese(II).

Macrocyclic complexes of Mn(II) were synthesized by template condensation using 2,6-diaminopyridine and diethylenetriamine with malonic, succinic, glutaric and adipic acids. The reaction proceeded smoothly to completion. These 16- to 24-membered N(6), but behaving as tetradentate, macrocyclic complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, mass and X-ray spectral analyses. The elemental analyses are consistent with the formation of complexes [Mn(N(6)L(n))Cl(2)]. All the complexes are stable and monomeric in nature, as indicated by the molecular weight determinations. The spectral studies confirmed the proposed framework of the new macrocyclic complexes and indicated an octahedral geometry around the central metal atom. The complexes were screened in vitro against a number of pathogenic fungi and bacteria to assess their growth-inhibiting potential. The testicular sperm density, sperm morphology, sperm motility, density of cauda epididymis, spermatozoa and fertility in mating trials and the biochemical parameters of the reproductive organs of the rat were examined and are discussed.

Paraganglioma of the cauda equina: a case report and review of the literature.

This case report describes a paraganglioma of the cauda equina in a 57-year-old man. The clinical and pathological features of the 70 cases reported to date are reviewed. The importance of total surgical removal is stressed.

Primary ectopic intramuscular meningioma of the thigh.

A case of a primary ectopic intramuscular meningioma of the thigh in a 20-year-old male patient is presented. The possible histogenesis of primary ectopic meningiomas is summarized.

Spinal intramedullary cavernous angioma in a patient with Down's syndrome.

A rare case of cervical intramedullary cavernous angioma in a 30-year-old man with Down's syndrome is presented. A review of the literature showed this to be the first reported case. Magnetic resonance imaging was diagnostic. A myelotomy was done and multiple biopsies were taken. The patient deteriorated neurologically and later died due to severe chest infection. The presentation, management and prognosis of this condition are discussed.

Malignant schwannoma of the cerebellum: case report.

A case of malignant cerebellar schwannoma is presented in a woman aged 61 years. A malignant schwannoma of the cerebellum has not been previously reported in the literature. The histological, immunocytological, and ultrastructural properties suggested that this lesion was a malignant, partially epithelioid schwannoma.

Numerous giant mollusca contagiosa and kaposi's sarcomas with HIV disease.

A 50-year old man with a history of multiple contacts with commercial sex workers and two episodes of blood transfusions in Bombay, presented with giant mollusca contagiosa, Kaposi's sarcomas and refractory pulmonary tuberculosis. Patient was confirmed to be infected with HIV by ELISA and Western blot method.

Psoriasis in identical twins: simultaneous occurrence on same sites.

A pair of 12-year-old identical male twins presented to us with dull erythematous plaques with coarse scaling and deep fissuring over soles of both feet starting simultaneously 18 months ago. The diagnosis of psoriasis was confirmed by histopathological examination of the biopsy specimen.

Unilateral darier's disease.

Various variations of Darier's disease have been mentioned in the literature. Here we describe a young male with unilateral involvement with clinical and histopathological features typical of Darier's disease.