Synthesis and evaluation trypanosomicidal activity of new derivatives of megazol

Objective: This work aims at the synthesis of megazol analogs with antitrypanosomicidal activity. Chagas’disease is caused by Trypanosoma cruzi and is a debilitating disease that has both acute and chronic forms. Many South Americans suffer from the chronic form of Chagas’disease, and there is no treatment currently available.Methods: In the chemical part, classical techniques of heterocyclic synthesis as well as usual methods of identification were used. In the biological part the cell proliferation test was used in vitro and the IC 50.Results: We synthesized a series of derivatives of 2-(1-methyl-5-nitro-2-imidazolyl)-5-substituted-1,3,4-thiadiazoles where 1-acetyl, 1-propyl and 1-nonyl were used as the substituent (4,6,7). Derivatives without nitro group were also synthesized (3,12) along with thiosemicarbazones (8,9,10) and a 5-(5-nitro-2-furanyl)-1,3,4-thiadiazol-2-amine (11). These compounds were evaluated using an in vitro test where were measured the cell proliferation. The derivatives that obtained the best results underwent further tests, in which their IC50 was calculated. The data revealed that two compounds (4,6) were effective against the parasite (IC50= 0.354 µM; IC50= 2.13 µM) and besides that, obtained the same results as the positive control, antimycim and rotenone. All proposed structures were obtained in satisfactory yields and purities.Conclusions: In conclusion, the in vitro trypanocidal activity makes these compounds promising leads in the development of an effective therapeutic agent. However, this study must be completed by additional tests with in vitro amastigote/macrophage models or in vivo mouse models. Analyzing the amide derivatives, compounds (4) and (6) were the ones that presented the best results.

Evaluation of analgesic activity of ethanolic and aqueous extracts of leaf of Plumeria rubra in albino rat

Objective: Plumeria rubra is an important traditional medicinal plant used in various ailments and the indigenous plant as a medicament for treatment of various inflammatory conditions is well documented in literature. The analgesic activity was evaluated by hot-plate and acetic acid induced writhing methods.Methods: The leaves of P. rubra were collected from the local area in and around Palakkad, Kerala (India). About 1500 g of the powder was extracted using Soxhlet apparatus for 12 h using 5.0 L of Ethanol as solvent. The test extracts was administered intraperitoneally at a dose of 100 and 200 mg/kg while Pentazocine (5 mg/kg) and diclofenac sodium (10 mg/kg) served as standards.Results: The ethanolic extract of 200 mg/kg having significant analgesic activity in Acetic acid induced abdominal writhing response and percentage of inhibition (PI) (p<0.01 )when compared to control.. The Ethanolic extract of 100 mg/kg and 200 mg/kg exhibited significant analgesic activity in the hot plate method (p<0.001) by increasing the pain reaction time (PAT) of the rats to sec 7.25±0.38 at 45 min after treatment in comparison to control (4.08±13).Conclusions: The results suggest that ethanolic extracts of P. rubra possesses potent analgesic properties, which support its use in traditional medicine and suggesting that the plant should be further investigated for its pharmacological active natural products.

Polycystic ovarian syndrome: a curse to young women’s

The endocrine system is the group of glands that secrete hormone directly into the circulatory system moves towards distant target organs and affects them. This system release hormones that help control many important body functions. Dysfunctioning in the endocrine system may develop many disorders like diabetes, thyroid, growth disorders and sexual dysfunction. Poly cystic ovarian syndrome is one of the common endocrine disorder. PCOS is a common condition that causes a range of symptoms including irregular periods, unwanted hair growth, acne and weight problems. Increased circulating levels of testosterone can be considered as the major cause of development of polycystic ovarian syndrome. It is a male hormone, but women’s bodies make it too. Higher than normal testosterone level, makes women to experience PCOS. The physicians target on regular menstruation. In order to maintain the regular periods physicians basically administer Estrogen and Progesterone injection. Metformin is used during PCOS to treat insulin resistance developed in those women. Insulin resistance means that their bodies do not respond well to the hormone insulin that controls blood sugar levels. This causes blood sugar level to rise and this may lead to greater production of testosterone. Corticosteroids, vitamins, contraceptives pills are also prescribed for symptomatic treatment of PCOS. Changing of lifestyles may greatly help in management of poly cystic ovarian disorder. Regular exercise and weight management is the key for complete treatment of PCOS. This review contains all the information regarding PCOS.

Molecular structure, HOMO, LUMO, MEP, natural bond orbital analysis of benzo and anthraquinodimethane derivatives

Objective: Optimized molecular structures have been investigated by DFT/B3LYP method with 6-31G (d,p) basis set. Stability of Benzo and anthraquinodimethane derivatives 1-4, hyperconjugative interactions, charge delocalization and intramolecular hydrogen bond has been analyzed by using natural bond orbital (NBO) analysis. Electronic structures were discussed and the relocation of the electron density was determined. Molecular electrostatic potential (MEP), local density functional descriptors has been studied. Nonlinear optical (NLO) properties were also investigated. In addition, frontier molecular orbitals analyses have been performed from the optimized geometries. An ionization potential (I), electron affinity (A), electrophilicity index (ω), chemical potential (µ), electronegativity (χ), hardness (η), and softness (S), have been investigated. All the above calculations are made by the method mentioned above.Methods: The most stable optimized geometries obtained from DFT/B3LYP method with 6-31G(d,p) basis set were investigated for the study of molecular structures, nonlinear properties, natural bond orbital (NBO), molecular electrostatic potential (MEP) and frontier molecular orbital of Benzo and anthraquinodimethane derivatives.Results: Reactive sites of electrophilic and nucleophilic attacks for the investigated molecule were predicted using MEP at the B3LYP/6-31G(d,p). Compound 4 possesses higher electronegativity value than all compounds so; it is the best electron acceptor; the more reactive sites for electrophilic attacks are shown in compounds 1 and 4, for nucleophilic attacks are indicated in compounds 2 and 3 and the more reactive sites in radical attacks are detected in compounds 2 and 4.Conclusions: Compound 1 is softest, best electron donor and more reactive than all compounds. The calculated first order hyperpolarizability was found much lesser than reported in literature for urea.

Development and statistically validated UV spectrophotometric determination of testosterone in gel formulation

Objective: A simple, precise and accurate UV-spectrophotometric method is developed and statistically validated for estimation of Testosterone in gel formulation. The proposed method includes using regression equation, area under curve (AUC), first order derivative and second order derivative spectroscopic method.Methods: based on measurement of absorbance at a selected wavelength using UV-visible spectrophotometer with 1cm matched quartz cell and acetonitrile as a solvent. All developed methods obeyed Beer’s-lambert’s law in the concentration range of 5-25μg/mL, with correlation coefficient value less than 1.Results: The percent amount of drug estimated was nearly 100%, found to be a good agreement with label claim of marketed gel formulation. The recovery study was carried out at three different levels, the validation study data was found to be statistically significant as all the statistical parameters are within the acceptance range (% RSD <2.0 and S.D. <±2.0).Conclusions: The results of estimation and validation parameters like accuracy, precision, ruggedness, linearity and range were studied for all the developed methods and were found to be within limits. The results obtained were statistically compared using paired t-test and one way ANOVA analysis. The proposed method can be adopted for routine quality control for estimation of drug in formulation.

Comparative efficacy of herbal anti-diarrheal products for treatment of diarrhea in calves

Objective: The present study was undertaken to compare the efficacy of herbal drugs, Diaroak® and Salcochek® (M/s Ayurvet Limited), against antibiotic drugs in the treatment of calf diarrhea.Methods: 15 calves suffering from diarrhea were divided into 3 groups: T0,receiving ciprofloxacin (250 mg) and tinidazole (300 mg) twice daily for three days, T1, receiving 15 gm Diaroak twice daily till recovery, and T3, receiving 15 gm Salcochektwice daily till recovery. The parameters evaluated included average number of doses required for complete recovery, total number of animals completely recovered per group, number of animals in morbid state per group, mortality recorded per group, frequency of defecation per group, presence or absence of mucus in feces along with appetite of animals, and incidence of diarrhea and mortality during post-treatment period.Results: Complete recovery was seen in all the treated animals with no recurrence. After recovery, animals treated with herbals had better consistency of feces than those treated with antibiotics.Conclusions: Herbal anti-diarrheals Diaroak and Salcocheck can be used for treating non-specific diarrhea in calves.

Cephalosporins: pharmacology and chemistry

Cephalosporins are the most important antibiotics having β-lactam ring and are obtained from a fungus Acremonium, also known as cephalosporium. The wide use of cephalosporins against bacteria in various severe infections such as respiratory tract infection (RTI), skin infection and urinary tract infection (UTI) has led the scientist dive into the detail of this antibacterial drug. The knowledge about structural activity relationship (SAR), spectrum of inhibition (SOI), chemical properties and pharmacology of cephalosporin has pivotal impact to device advanced therapeutic results. The treatment of a disease using cephalosporin has many pros and cons. If the pharmacology and chemical properties of this drug are known properly, many side effects can be diminished or minimized to a certain level. This article review some pharmacological and chemical properties of cephalosporins.

Synthesis and biological evaluation of new aryl substituted Schiff’s bases

Objective: Chemical substances employed to treat various infections caused by various types of microorganism are termed as antimicrobials and natural chemical compounds produced by specific types of bacteria are termed as antibiotics. Unlimited use of antibiotics in humans and animals and in areas other than the treatment and prophylaxis of disease have resulted in a serious problem of drug resistance. Various attempts have been adopted to cope with the resistance problem and enhance the activity, or broaden the spectrum of drugs. Based on structure-activity relationship synthesis of new compounds has been one of the best approaches for better results. It has been demonstrated that Schiff base of some leading molecules and antibiotics possess good potential as more effective and safe drugs. Encouraged by reports on potential of Schiff’s bases as antimicrobial agents and to cope up with the current requirements of developing newer, safer and broad spectrum agents attempts were made to synthesize new Schiff’s bases.Methods: Our earlier in which structure activity relationship studies revealed that substitution by nitro and amino gp in Schiff’s base moiety resulted in the enhancement of activity. So further attempts were made to extend the series with incorporation of nitro and amino moiety by condensing o,m dinitro substituted acid hydrazide with various nitro/amino substituted benzaldehydes for increasing their antimicrobial potential.Results: Synthesized compounds were characterized on the basis of spectral studies (like UV, IR, and NMR). All the synthesized derivatives were screened further for their antibacterial effect. All the synthesized derivatives were screened further for their antibacterial effect.Conclusions: Highest activity was observed in the derivative with nitro substitution in both the aryl rings.

Effect of lopinavir and efavirenz on pharmacokinetics and pharmacodynamics of glibenclamide in diabetic rats

Objective: The aim of the study is whether the impact of Efavirenz and Lopinavir will increase the plasma level of Glibenclamide or not. Efavirenz and Lopinavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450-3A4. Multiple CYP isoforms are involved in the metabolism of Glibenclamide like CYP2C8 and CYP3A4. Hence there is more possibility of Efavirenz and Lopinavir to inhibit the metabolism of Glibenclamide by inhibiting CYP 3A4.Methods: Efavirenz and Lopinavir (10 mg/kg,p.o.) alone and along with Glibenclamide (10 mg/kg, p.o.) was given to normal and diabetic rats. PK/PD parameters were studied. In the rats co-treated with Efavirenz and Lopinavir and Glibenclamide.Results: The pharmacokinetic parameters like clearance of Glibenclamide was reduced, peak plasma concentration, area under the plasma concentration time curve and elimination half-life were significantly increased when compared to pioglitazone treated rats.Conclusions: This study revealed that lopinavir and efavirenz affected the disposition of Glibenclamide in rats probably by the inhibition of CYP3A4, leading to increasing Glibenclamide concentrations that could increase the efficacy of Glibenclamide or it may causes severe hypoglycemia. Therefore, its warrants to use relatively less dose of Glibenclamide than the normal dose.

Antimicrobial evaluation of flowering stalks of Cistanche violacea, a holoparasitic plant collected from arid region in Qassim, Saudi Arabia

Objective: Cistanche violacea has been found in Qassim region (Saudi Arabia), growing as a parasitic plant on Haloxylon salicornicum. The flowering stalk part of this plant was evaluated for antimicrobial potential against various referenced bacteria and fungi.Methods: The flowering stalk parts were collected from the field, dried, extracted by maceration in 80% methanol and 80% Ethanol, The crude extracts were examined against the tested microorganisms using agar-well diffusion method.Results: The antimicrobial testing showed that among 10 referenced bacterial isolates, only one exhibited significant susceptibility to the methanol and ethanol extracts of C. violacea, which was Staphylococcus epidermidis ATCC® 12228TM, recorded 15 and 16 mm inhibition zones, respectively. While other bacteria recorded weak or no susceptibility and no antifungal activity was detected.Conclusions: In general, the methanolic and ethanolic extracts of the flowering stalks of C. violacea exhibited weak or no antimicrobial properties except with one bacterial strain, further studies on the other biological activities are recommended as well as investigating the chemical constituents. To the best of the author’s knowledge, this is the first report evaluating the antimicrobial potential of the flowering stalks of C. violacea in Qassim area, Saudi Arabia.