New route to ABCD-porphyrins via bilanes

A new strategy for preparing porphyrins that bear up to four different meso-substituents (ABCD-porphyrins) relies on two key reactions. One key reaction entails a directed synthesis of a 1-protected 19-acylbilane by acid-catalyzed condensation at high concentration (0.5 M) of a 1-acyldipyrromethane and a 9-protected dipyrromethane-1-carbinol (derived from a 9-protected 1-acyldipyrromethane). Three protecting groups (X) were examined, including thiocyanato, ethylthio, and bromo, of which bromo proved most effective. The bilanes were obtained in 72-80% yield, fully characterized, and examined by 15N NMR spectroscopy. The second key reaction entails a one-flask transformation of the 1-protected 19-acylbilane under basic, metal-templating conditions to give the corresponding metalloporphyrin. The reaction parameters investigated for cyclization of the bilane include solvent, metal salt, base, concentration, temperature, atmosphere, and time. The best conditions entailed the 1-bromo-19-acylbilane at 100 mM in toluene containing DBU (10 mol equiv) and MgBr2 (3 mol equiv) at 115 degrees C exposed to air for 2 h, which afforded the magnesium porphyrin in 65% yield. The magnesium porphyrin is readily demetalated to give the free base porphyrin. A stepwise procedure (which entailed treatment of the 1-(ethylthio)-19-acylbilane to oxidation, metal complexation, desulfurization, carbonyl reduction, and acid-catalyzed condensation) was developed but was much less efficient than the one-flask process. The new route to ABCD-porphyrins retains the desirable features of the existing "2 + 2" (dipyrromethane + dipyrromethane-1,9-dicarbinol) method, such as absence of scrambling, yet has significant advantages. The advantages include the absence of acid in the porphyrin-forming step, the use of a metal template for cyclization, the ability to carry out the reaction at high concentration, the lack of a quinone oxidant, avoidance of use of dichloromethane, and the increased yield of macrocycle formation to give the target ABCD-metalloporphyrin.     

A numerical and analytical approach for exploration of entropy generation in Sisko nanofluid flow having swimming microorganisms

Journal of Thermal Analysis and Calorimetry - A new system of equations is developed using Galerkin finite element scheme for the investigation of the generation of entropy in viscoelastic Sisko...     

Atomic absorption and inductively coupled plasma–optical emission spectroscopic method for determination of micronutrients and toxic metals in Curcuma longa L. to characterize human health toxicity

Environment-friendly procedures for determination of nutritious and harmful elements in curcuma longa L. and commercially available turmeric powder are presented. Microwave and ultrasound (probe and bath) procedures for sample preparations were adopted and the elements were determined by validated flame atomic absorption and inductively coupled plasma–optical emission spectrometry. Student’s t-test was established whether there was a difference between the sample preparation methods. Trueness of certified values by all methods was ensured which were not differing significantly at 95% level of confidence interval. % recovery and relative standard deviation are in compliance with Food and Drug Administration-USA guidelines for spectrometric determination of elemental composition in food stuffs. Results showed that concentrations of copper, iron, manganese, and zinc found in both types of samples are promising source of nutrition. Exposure to aluminum, cadmium, and lead from consumption of products under investigation was estimated and few sample contents were higher than permissible level suggested by Food and Agriculture Organization-UN. Regarding the food safety monitoring, the proposed methods are rapid and met green chemistry approach can be implemented in laboratories easily for routine analysis.     

Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5–6 and 8a–8b. The compound 5 exhibits an exceptional IC₅₀ value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.     

Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 mM) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0.65 mM) and calcium channel blockers, diltiazem (IC50 = 13 mM) and verapamil (IC50 = 18 mM). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 mM), a cyclooxygenase inhibitor (indomethacin; IC50 = 0.2 mM) and inhibitor of TLCK, herbimycin A with IC50 value of 5 mM. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 mM. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways.     

Determination of macronutrients,micronutrients, non-essential elements in milk based-infant formulas by atomic absorption and inductively coupled plasma-optical emission spectroscopy after microwave and ultrasound assisted digestion

Microwave and ultrasound procedures for samples preparations were adopted and the elements were determined by validated flame atomic absorption and inductively coupled plasma–optical emission spectrometry. Student’s t-test was established whether there was a difference between the sample preparation methods. Trueness of certified values by all methods was ensured which were not differing significantly at 95% level of confidence interval. The highest intensity ratio of magnesium (II)/magnesium (I) was obtained at 1120 radiofrequency value to achieve accurate and reproducible results by inductively coupled plasma–optical emission spectrometry. The value of corresponding correlation coefficient (r²) were obtained as >0.990 indicating the excellent linearity for concentration range chosen for each element to be determined in commercial samples. Results showed that concentrations of calcium, magnesium, potassium, sodium, chromium, copper, iron, manganese, selenium, and zinc found in commercially available products are in good agreement with label as declared by the manufacturers. Exposure to aluminum, cadmium, and lead from consumption of products under evaluation was estimated and it was in compliance with permissible level suggested by European Commission regulations. Regarding the food safety monitoring, the proposed methods are rapid and met green chemistry approach so that can be implemented in laboratories easily for routine analysis.     

Two new triterpenoids and a steroidal glycoside from the aerial parts of Ocimum basilicum

Studies on the chemical constituents of the aerial parts of Ocimum basilicum have led to the isolation of three new compounds, basilol (1), ocimol (2), and basilimoside (3), along with two known constituents betulinic acid and oleanolic acid. The structures of the new constituents have been elucidated through spectral studies including 2D-NMR experiments (HMQC, HMBC, COSY, NOESY, and J-resolved) and chemical transformation, as p-formylphenyl 3beta-hydroxyolean-12-en-28-oate (1), 2-methoxy-4-carbomethoxyphenyl 3beta-hydroxy-lup-20(29)-en-28-oate (2), and (22E)-24xi-ethyl-25-methylcholesta-5,22-diene-3beta-ol-3-O-D-glucopyranoside (3).     

Preparation & characterization of embelin�Cphospholipid complex as effective drug delivery tool

The aim of the present study was to prepare an embelin?Cphospholipid complex (EPC) formulation in an attempt to enhance the water solubility and to characterize the new developed formulation. Embelin, due to water insolubility causes poor bioavailability by oral route. To improve the bioavailability and prolong its duration in body system, its phospholipid complexes were prepared by a simple and reproducible method. EPC was formulated by mechanical dispersion method using ethanol as a reaction medium, embelin and phospholipids were dissolved into the medium, after that organic solvent was removed under vacuum condition and EPC was formed. The complex formation was confirmed by carrying out FTIR, ¹H-NMR, XRD, DSC and microscopical studies. Solubility and in vitro studies were carried out to ascertain the solubility and dissolution pattern of free and complexed embelin. Content of embelin in EPC was found to be 92.44% (w/w). FTIR, ¹H NMR, DSC and XRD data confirmed the formation of embelin phospholipid complex. Water solubility of embelin was improved from 3 to 42 ??g/mL in the prepared complex. n-Octanol solubility were also altered for free embelin and EPC from 2.3 to 39 ??g/mL. Unlike the free embelin, which showed a total of only 19% drug release at the end of 120 min, EPC showed 99.80% release at the end of 120 min of dissolution study in distilled water. Microscopical characterization of the developed formulation also showed the entrapment of embelin in the lipid core showing complex structure, which was further, supported by change in surface morphology of embelin on microscopical examination. Hence, the present findings demonstrate that complexing embelin with phospholipid can be further explored for improved therapeutic implications.     

Potent anti-platelet constituents from Centaurea iberica

New naturally occurring nitrogenous compounds 1 and 2, along with a new dimeric lignan glucoside 3, have been isolated from the ethyl acetate soluble fraction of Centaurea iberica. Their structures have been elucidated through spectroscopic techniques. All the isolated compounds showed significant platelet aggregation inhibition.