Comprehensive Study on Solomonamides: Total Synthesis, Stereochemical Revision, and SAR Studies toward Identification of Simplified Lead.

Solomonamides, a pair of macrocyclic peptide natural products originating from marine sources, have garnered significant attention within the synthetic community owing to their marked anti-inflammatory efficacy and intricate molecular architectures. In this paper, we present a very detailed investigation into solomonamides, including the challenges associated with the total synthesis, the evolution of our synthetic strategies, structural reassignment, synthesis of all possible stereoisomeric macrocycles, biological assessment, structure-activity relationship (SAR) studies, etc. Within the ambit of this total synthesis, diverse strategies for macrocyclization were rigorously explored, encompassing the Friedel-Crafts acylation, cyclization involving the aniline NH2 moiety, macrolactamization utilizing Gly-NH2, and Heck macrocyclization methodologies. In addition, an array of intriguing chemical transformations were devised, including but not limited to photo-Fries rearrangement, Wacker oxidation, ligand-free Heck macrocyclization, oxidative cleavage of indole, synthesis of contiguous stereocenters via substrate/reagent-controlled protocols, and simultaneous making and breaking of olefinic moieties. The findings of this investigation revealed a structurally simplified lead compound. Remarkably, the lead compound, while possessing structural simplification in comparison to the intricate solomonamide counterparts, demonstrates equipotent in vivo anti-inflammatory efficacy.

Synthesis, biological evaluation and docking studies of silicon incorporated diarylpyrroles as MmpL3 inhibitors: An effective strategy towards development of potent anti-tubercular agents.

Growing global demand for new molecules to treat tuberculosis has created an urgent need to develop novel strategies to combat the menace. BM212 related compounds were found to be potent anti-TB agents and they inhibit mycolic acid transporter, MmpL3, a known potent drug target from Mycobacterium tuberculosis. In order to enhance their inhibitory potency, several silicon analogues of diarylpyrroles related to BM212 were designed, synthesized, and evaluated for anti-tubercular activities. In Alamar blue assay, most of the silicon-incorporated compounds were found to be more potent than the parent compound (BM212), against Mycobacterium tuberculosis (MIC = 1.7 µM, H37Rv). Docking results from the crystal structure of MmpL3 and silicon analogues as pharmacophore model also strongly correlate with the biological assays and suggest that the incorporation of silicon in the inhibitor scaffold could enhance their potency by stabilizing the hydrophobic residues at the binding pocket. The best docking hit, compound 12 showed an MIC of 0.1 µM against H37Rv with an acceptable in vitro ADME profile and excellent selectivity index. Overall, the present study indicates that, the designed silicon analogues, especially compound 12 could be a good inhibitor for an intrinsically flexible drug-binding pocket of MmpL3 and has potential for further development as anti-tubercular agents.

Application of Vinamidinium Salt Chemistry for a Palladium Free Synthesis of Anti-Malarial MMV048: A "Bottom-Up" Approach.

MMV390048 (1) is a clinical compound under investigation for antimalarial activity. A new synthetic route was developed which couples two aromatic fragments while forming the central pyridine ring over two steps. This sequence takes advantage of raw materials used in the existing etoricoxib supply chain and eliminates the need for palladium catalysts, which were projected to be major cost-drivers.

A concise route to MK-4482 (EIDD-2801) from cytidine.

A two-step route to MK-4482 (EIDD-2801, 1) was developed consisting of an esterification and hydroxamination of cytidine. The selective acylation and direct amination eliminate the need for protecting and activating groups and proceed in overall yield of 75%, a significant advancement over the reported yield of 17%. The step count is reduced from five transformations to two, and expensive uridine is replaced with the more available cytidine.

Efficient Image De-Noising Technique Based on Modified Cuckoo Search Algorithm.

The image restoration has emerged as a very vital investigation technique in the domain of the image processing. The underlying motive behind the image restoration is devoted to the augmentation of the perceived visual impact of image so as to make it almost identical to the original image. A host of exploration approaches are now in vogues which are intended to steer clear of the noise, thereby regaining the images with original quality. In our earlier research, two distinct noise elimination methods like the (OGHP) and SURE shrinkage were effectively employed for the purpose of denoising, though the relative PSNR and SSIM efficiencies did not come up to the desired level. In the innovative approach envisaged in the document, at the outset, the noise is included by means of two processes like the salt and pepper and impulse noise. Subsequently, the pre-processing methods are performed with the able assistance of two novel filters such as the adaptive median filter and adaptive fuzzy switching. Thereafter, the preprocessed image is furnished to the succeeding function of noise elimination like the (OGHP) and SURE shrinkage. In the course of the OGHP noise elimination technique, the GHP constraints are optimized by employing the Cuckoo Search Algorithm. Thereafter, the noise-eliminated image is effectively estimated with the help of the Discrete Wavelet Transform (DWT). The consequential noiseless images are subjected to the image restoration procedure by efficiently employing the AGA approach. The cheering performance outcomes chant the success stories of the novel image restoration method, highlighting its superlative efficiency. Moreover, the efficacy of the innovative approach is assessed by means of a set of noise-polluted images and contrasted with the modern noiseless image restoration technique.

Repurposing Ivacaftor for treatment of Staphylococcus aureus infections.

Drug repurposing of non-antimicrobials is a novel method to augment a seriously depleted drug pipeline for targeting drug-resistant pathogens. This article highlights the potent antimicrobial activity of Ivacaftor against Staphylococcus aureus, including vancomycin- and other multidrug-resistant strains. The potent activity of Ivacaftor in vivo is also demonstrated in a murine neutropenic thigh infection model. Taken together, these results support the potential of Ivacaftor as an antimicrobial agent for the treatment of staphylococcal infections.

Impact of heavy metal toxicity and constructed wetland system as a tool in remediation.

The objective of this review is to throw light upon the global concern of heavy metal-contaminated sites and their remediation through an ecofriendly approach. Accumulated heavy metals in soil and water bodies gain entry through the food chain and pose serious threat to all forms of life. This has engendered interest in phytoremediation techniques where hyperaccumulators are used. Constructed wetland has a pivotal role and is a cost-effective technique in the remediation of heavy metals. Metal availability and mobility are influenced by the addition of chelating agents, which enhance the availability of metal uptake. This review helps in identifying the critical knowledge gaps and areas to enhance research in the future to develop strategies such as genetically engineered hyperaccumulators to attain an environment devoid of heavy metal contamination.

Total synthesis of Deoxy-solomonamide B by mimicking biogenesis.

A total synthesis of Deoxy-solomonamide B was accomplished starting from tryptophan in an efficient manner by mimicking the proposed biogenetic route. The present synthesis utilizes a crotylation, oxidative cleavage of the indole moiety, and macrolactamization as key steps. The use of the indole nucleus as a masked anthranilic acid unit paves the way for the easy synthesis of related macrocycles and natural products where the ortho-acyl aniline moiety is embedded into them, which otherwise is difficult to synthesize.

Studies toward the synthesis of potent anti-inflammatory peptides solomonamides A and B: synthesis of a macrocyclic skeleton and key fragment 4-amino-6-(2'-amino-4'-hydroxyphenyl)-3-hydroxy-2-methyl-6-oxohexanoic acid (AHMOA).

A first synthetic effort toward total synthesis of highly potent solomonamides is disclosed. An efficient strategy to synthesize this class of compounds, along with the synthesis of a core macrocycle (shown in red) and the key fragment AHMOA, is described.

Biodegradation of polycyclic aromatic hydrocarbons by a halotolerant bacterial strain Ochrobactrum sp. VA1.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants in the environment and are derived from both man-made and natural resources. The present study is focused on the degradation of PAHs by a halotolerant bacterial strain under saline conditions. The bacterial strain VA1 was isolated from a PAH-degrading consortium that was enriched from marine water samples that were collected from different sites at Chennai, India. In the present study, a clearing zone formed on PAH-amended mineral salt agar media confirmed the utilization of PAH by the bacterial strain VA1. The results show that the strain VA1 was able to degrade anthracene (88%), phenanthrene (98%), naphthalene (90%), fluorene (97%), pyrene (84%), benzo(k)fluoranthene (57%) and benzo(e)pyrene (50%) at a 30 g/L NaCl concentration. The present study reveals that the VA1 strain was able to degrade PAHs in petroleum wastewater under saline conditions. The promising PAH-degrading halotolerant bacterial strain, VA1, was identified as Ochrobactrum sp. using biochemical and molecular techniques.

Decolourisation of azo dye, Acid Red-18 by Phanerochaete chrysosporium.

The ability of wood rotting fungus, Phanerochaete chrysosporium to decolourise azo dye, Acid Red -18 was investigated. The optimal parameters (pH and cell load) required for effective decolourisation were determined. The strain was capable of decolourising dye over a pH range of 4-6 and decolourisation was rather fast, more than 90% in all cases. The optimal pH 5 and cell load of 2.4 x 10(6) spores/mL is required for complete decolourisation of 100 micromol of azo dye Acid Red-18 at a temperature of 37 degrees C. The fungus proved to be capable of both biodegradation and biosorption, and biosorption was found to be the major dye removal mechanism.

Role of a moderately halophilic bacterial consortium in the biodegradation of polyaromatic hydrocarbons.

Polycyclic aromatic hydrocarbons are ubiquitous pollutants in the environment, and most high molecular weight PAHs cause mutagenic, teratogenic and potentially carcinogenic effects. While several strains have been identified that degrade PAHs, the present study is focused on the degradation of PAHs in a marine environment by a moderately halophilic bacterial consortium. The bacterial consortium was isolated from a mixture of marine water samples collected from seven different sites in Chennai, India. The low molecular weight (LMW) PAHs phenanthrene and fluorine, and the high molecular weight (HMW) PAHs pyrene and benzo(e)pyrene were selected for the degradation study. The consortium metabolized both LMW and HMW PAHs. The consortium was also able to degrade PAHs present in crude oil-contaminated saline wastewater. The bacterial consortium was able to degrade 80% of HMW PAHs and 100% of LMW PAHs in the saline wastewater. The strains present in the consortium were identified as Ochrobactrum sp., Enterobacter cloacae and Stenotrophomonas maltophilia. This study reveals that these bacteria have the potential to degrade different PAHs in saline wastewater.

Role of plasmid in the degradation of petroleum hydrocarbon by Pseudomonas fluorescens NS1.

In this study the role of plasmid in Pseudomonas fluorescens, isolated from petroleum contaminated soil on hexadecane degradation was assessed. The organism was able to utilize hexadecane as sole carbon source and also reduce surface tension up to 27 mN/m. The organism harboured a plasmid of approximately 1.8 kb. Plasmid curing and transformation of plasmid DNA into E. coli revealed that the plasmid was involved in hexadecane degradation. When compared to P. fluorescens, no significant growth was observed with wild-type E. coli strain. P. fluorescens degraded 95% of hexadecane (0.4% (v/v)) whereas the transformed strain degraded 92% of hexadecane in 120 h, which was almost equivalent to the degradation by P. fluorescens. The wild-type E. coli showed no significant degradation of hexadecane whereas, the plasmid transformed E. coli was able to degrade hexadecane, which indicates the expression of the catabolic genes in the transformed E. coli strain.

Organochlorine pesticide residues in ground water of Thiruvallur district, India.

Modern agriculture practices reveal an increase in use of pesticides and fertilizers to meet the food demand of increasing population which results in contamination of the environment. In India crop production increased to 100% but the cropping area has increased marginally by 20%. Pesticides have played a major role in achieving the maximum crop production, but maximum usage and accumulation of pesticide residues was highly detrimental to aquatic and other ecosystem. The present study was chosen to know the level of organochlorines contamination in ground water of Thiruvallur district, Tamil Nadu, India. The samples were highly contaminated with DDT, HCH, endosulfan and their derivatives. Among the HCH derivatives, Gamma HCH residues was found maximum of 9.8 microg/l in Arumbakkam open wells. Concentrations of pp-DDT and op-DDT were 14.3 microg/l and 0.8 microg/l. The maximum residue (15.9 microg/l) of endosulfan sulfate was recorded in Kandigai village bore well. The study showed that the ground water samples were highly contaminated with organochlorine residues.

Persistence and distribution of endosulfan under field condition.

Rapid increase in industrialization and agricultural activities to meet the population need has led to environmental pollution. The major revolution in agricultural production is mainly due to increased use of pesticides and fertilizers. Soil act as a major sink for majority of pesticides applied on agricultural crops. Among the organochlorines, endosulfan is the most commonly used pesticide, hence this study concentrates on the persistence and distribution behaviour of endosulfan under field conditions. The result showed that the alpha endosulfan concentrations were very minimum (0.98 mg/kg of soil) in all the four fields under study (Nazarath, Othikadu, Ekkadu and Ekkadukandigai of Thiruvallur district, Tamil Nadu). Where as beta endosulfan concentration at the time of application was 6.39 mg/kg and declined to 0.8 mg/kg on soil at 150th day. The endosulfan sulfate concentration was 11.8 mg/kg in soil at 15th day and then concentration declined to 2.2 mg/kg at 150th day. Field run-off samples showed maximum residue levels (0.024 mg/l) at the early irrigation period. While plant foliar parts showed maximum concentrations of alpha-endosulfan (43.4 mg/kg), beta-endosulfan (40.6 mg/kg) and endosulfan sulfate (20.1 mg/kg). At harvest stage, rice grain and husk also had lower concentrations of endosulfan sulfate (2.2 and 0.09 mg/kg), respectively.

Microbial diversity in hypersaline wastewater: the example of tanneries.

In contrast to conventional wastewater treatment plants and saline environments, little is known regarding the microbial diversity of hypersaline wastewater. In this study, the microbial communities of a hypersaline tannery effluent, and those of three treatment systems operating with the tannery effluent, were investigated using 16S rDNA phylogenetic markers. The comparative analysis of 377 bacterial sequences revealed the high diversity of this type of hypersaline environment, clustering within 193 phylotypes (> or = 97% similarity) and covering 14 of the 52 divisions of the bacterial domain, i.e. Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, Chlorobi, Planctomycetes, Spirochaetes, Synergistes, Chloroflexi, Thermotogae, Verrucomicrobia, OP3, OP11 and TM7. Most of the phylotypes were related to halophilic and pollutant-degrading bacteria. Using statistical analysis, the diversity of this type of environment was compared to that of other environmental samples selected on the basis of their salinity, oxygen content and organic load.

Anaerobic digestion of tannery soak liquor with an aerobic post-treatment.

The leather industry occupies a place of prominence in the Indian economy due to its massive potential for employment, growth and exports. The potential environmental impact of tanning is significant. This study focuses on tannery soak liquor, generated by the soaking of hides and skins, which is characterised by high organic load and high salinity. For these reasons, the soak liquor should be segregated and pre-treated separately before being mixed with the composite wastewater, made of all other streams mixed together. The anaerobic digestion of tannery soak liquor was studied using a UASB. COD removal reached 78% at an OLR of 0.5 kg COD m(-3) d(-1), a HRT of 5 days and a TDS concentration of 71 gl(-1). The combination of the UASB with an aerobic post-treatment enhanced the performance of the overall wastewater treatment process and the COD removal efficiency of the combined anaerobic/aerobic treatment system reached 96%. However, for effective operation, the system had to be operated at very low OLRs, which affects the economic viability of such a process.

Halophilic biological treatment of tannery soak liquor in a sequencing batch reactor.

Hypersaline wastewater (i.e. wastewater containing more than 35 gl(-1) total dissolved solids (TDS)) is generated by various industrial activities. This wastewater, rich in both organic matter and TDS, is difficult to treat using conventional biological wastewater treatment processes. Among the industries generating hypersaline effluents, tanneries are prominent in India. In this study, tannery wastewater from soak pit was treated in a lab-scale SBR for the removal of organic matter. The characterisation of the soak liquor showed that this effluent is biodegradable, though not easily, and highly variable, depending on the origin and the nature of the hides. TDS was in the range of 21-57 gl(-1) and COD was in the range of 1.5-3.6 gl(-1). This soak liquor was biologically treated in an aerobic sequencing batch reactor seeded with halophilic bacteria, and the performance of the system was evaluated under different operating conditions with changes in hydraulic retention time, organic loading rate and salt concentration. The changes in salinity appeared to affect the removal of organic matter more than the changes in hydraulic retention time or organic loading rate. Despite the variations in the characteristics of the soak liquor, the reactor achieved proper removal of organic matter, once the acclimation of the microorganisms was achieved. Optimum removal efficiencies of 95%, 93%, 96% and 92% on COD, PO4 3-, TKN and SS, respectively, could be reached with 5 days hydraulic retention time (HRT), an organic loading rate (OLR) of 0.6 kg COD m(-3)d(-1) and 34 g NaCl l(-1). The organisms responsible for nitrogen removal appeared to be the most sensitive to the modifications of these parameters.

Degradation of anthracene and pyrene supplied by microcrystals and non-aqueous-phase liquids.

Polycyclic aromatic hydrocarbons (PAHs) are worldwide environmental pollutants. Their bioavailability is limited by a low aqueous solubility, which causes specific adaptations in degrading bacteria. To compare bacterial degrading behavior, a study was conducted on the mineralization, metabolization and formation of biomass from (14)C-anthracene by Sphingomonas sp. BA2 compared with those from (14)C-pyrene by Gordonia-like strain BP9 and Mycobacterium gilvum VF1. Different conditions of PAH supply were used in the medium: crystals <0.5 mm, microcrystals <<0.1 mm formed by sonication, or PAH solubilized in 2,2,4,4,6,8,8-heptamethylnonane (HMN) or silicone oil. Anthracene supply by crystals and silicone oil led to similar maximum mineralization rates 33 ng ml(-1) h(-1) and the same amount of mineralization (24%) after 168 h. Microcrystals increased the rates and amounts only slightly. HMN decreased the values to less than one-third. In comparison with crystals, microcrystals increased overall pyrene mineralization by strain BP9 from 53% to 58%, with maximum mineralization rates of 160 ng ml(-1) h(-1) and 166 ng ml(-1) h(-1). Silicone oil heavily increased the rate to 292 ng ml(-1) h(-1) and the amount mineralized to 71%, whereas HMN inhibited the degradation by one order of magnitude. A similar degradation behavior showing lower mineralization rates and extent was observed with strain VF1. However, inhibition by HMN was less pronounced. Sonication, leading to decreased PAH crystal size, increased the mass transfer and mineralization rates. PAH supply by silicone oil led to a much higher mass transfer, which may be due to emulsification of the oil, whereas such effects were not observed with HMN.

Changes in fatty acid composition of Chromohalobacter israelensis with varying salt concentrations.

The adaptation of fatty acid composition of Chromohalobacter israelensis, a euryhalophilic bacterium, grown at different salt concentrations was studied. C. israelensis tolerated NaCl up to concentrations of 20% (w/v) and showed optimal growth at 7% (w/v). Major fatty acids of this bacterium were palmitic acid (16:0), stearic acid (18:0), palmetoleic acid (16:1cisDelta9), and cis-vaccenic acid (18:1Delta11). The salt concentration strongly influenced the fatty acid composition. In the presence of sub-optimal salt concentrations, the degree of saturation decreased, suggesting the importance of salt in maintaining the osmotic balance of the cell with its environment.