Jeetendra Kumar Gupta

Anti-inflammatory and antinociceptive evaluation of newly synthesized 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles

Introduction: 1,2,4-triazoles and its derivatives have been reported to possess anti-inflammatory, analgesic, antimicrobial, anticancer, antitumor, antitubercular, anticonvulsant, openers of Ca-activated potassium (Maxi-K) channels, antiviral properties, hypoglycemic, anxiolytic and antidepressant activity. Therefore, 1,2,4-triazole seems to be an important pharmacophore. Materials and Methods: The synthesis of 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) were prepared following six step starting 4-methoxy benzoic acid and using different secondary amines and were characterized with the help of FT-IR,1H,13C NMR, FAB Mass and nitrogen analysis. These synthesized compounds (6a-o) were then evaluated for anti-inflammatory activity by carrageenan induced paw edema method.Out of these synthesized compounds, some (6f, i and k) were evaluated for antinociceptive activity by Hot plate method and Tail immersion method. Results and Discussion: The synthesis of 4-(substituted amino)-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) was accomplished. The IR spectra exhibited characteristic bands for C-N, C=N, SH and C=O at 1350-1360, 1511-1548, 2520-2594.3 and 1650-1719 cm-1. The C-O-C asymmetric and symmetric str. was at 1250-1254 and 1027-1079.3 cm-1 respectively. In1H-NMR spectra, a singlet of CONH was found in the range of δ 9.92-10.18 ppm and another singlet of thiol group was observed in the range of δ 8.63-9.92 ppm. A singlet of Ar-OCH3 was also found between δ 3.57-3.91 ppm. In13 C- NMR spectra, C-3 and C-5 of the 1,2,4 - triazole nucleus were observed in the range of δ 147-166.9 ppm. Carbonyl carbon and methylene carbon of –NHCOCH2 N< were found between δ 166.5-177.5 and δ 47.1-62 ppm respectively. Acute toxicity study was donr following OECD-423 and cut-off dose was found to be between 1000-1500 mg/kg body weight. At the dose level of 100 mg/kg, 6f, 6i and 6k exhibited appreciable inhibition of oedema especially 6k exhibiting a percentage of oedema inhibition of 40.28%, which was comparable to that of the standard drug indomethacin (62.50% at 10mg/kg dose). Among the compounds tested, compound 6k exhibited good anti-nociceptive activity in both methods used. Pethidine (20mg/kg body weight s.c) is used as the standard drug. Conclusion: SAR of these synthesized compounds shows that substitution with heterocyclic moiety at C-2 of the acetamido group at position 4 of the 1,2,4-triazole produces appreciable activity as compared to substitution with aliphatic moieties since among all the synthesized compounds, the most active ones are 6f, 6i and 6k that have piperdine, 1-benzyl piperazine and morpholine group, respectively at C-2 of the acetamido group at position 4 of the 1,2,4-triazole.

Role of atrial natriuretic peptide in ischemic preconditioning–induced cardioprotection in the diabetic rat heart

BACKGROUNDnIt has been noted that nitric oxide (NO) is involved in the ischemic preconditioning (IPC)-mediated cardioprotection. Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in low expression of endothelial nitric oxide synthase (eNOS) by which NO level get reduced. The purpose of the present study was to investigate the role of ANP in attenuated cardioprotective effect of IPC in the diabetic rat heart.nnnMETHODSnThe heart was isolated from the diabetic rat and mounted on Langendorffs apparatus, subjected to 30-min ischemia and 120-min reperfusion. IPC was mediated by four cycles of 5-min ischemia and 5-min reperfusion. The infarct size was estimated using triphenyltetrazolium chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and creatinine kinase-MB release to assess the degree of myocardial injury. The cardiac release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent.nnnRESULTSnIPC-mediated cardioprotection was significantly attenuated in the diabetic rat as compared with the normal rat. Perfusion of ANP (0.1 μM/L) in the diabetic rat heart significantly restored the attenuated cardioprotective effect of IPC and also increased the release of NO. However, this observed cardioprotection was significantly attenuated by perfusion of N-nitro L-arginine methyl ester, an eNOS inhibitor (100 μM/L) noted in terms of increase in myocardial infarct size, release of lactate dehydrogenase and creatinine kinase-MB, and also decreases in release of NO.nnnCONCLUSIONSnThus, it is suggested that ANP restores the attenuated cardioprotective effect in the diabetic heart which may be due to increase in the expression of eNOS and subsequent increase in the activity of NO.

Synthesis of new 1,2,4-triazoles as anti-inflammatory and anti-nociceptive agents

A series of fifteen new substituted 1,2,4-triazoles (6a – 6o) have been synthesized in order to obtain new agents with potential anti-inflammatory and anti-nociceptive activity. The title compounds were synthesized using 4-methylbenzoic acid as a starting reactant. The synthesized compounds were characterized by spectroscopic methods (IR, 1H NMR, 13u2009C NMR, FAB+u2009−u2009MS) and elemental analysis (nitrogen analysis). The title compounds were evaluated for anti-inflammatory activity by the carrageenan induced paw edema method, and some compounds were evaluated for anti-nociceptive activity by the hot plate method and tail immersion method. Compounds N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-piperidin-1-ylacetamide (6f), 2-(4-benzylpiperazin-1-yl)-N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]acetamide (6i) and N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-morpholin-4-ylacetamide (6xa0k) showed significant anti-inflammatory activity compared to other synthesized compounds, and N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-morpholin-4-ylacetamide (6xa0k) exhibited superior anti-nociceptive activity.

Role of cardiac renin angiotensin system in ischemia reperfusion injury and preconditioning of heart

Cardio-vascular diseases are the leading cause of morbidity and mortality. Ischemia is a state of oxygen deprivation in tissues, whereas reperfusion is restoration of blood flow in ischemic tissues. Myocardial damage of tissue during reperfusion after ischemic insult is known as myocardial ischemia–reperfusion (I/R) injury. It induces damage to cardiac muscle via increasing expression of oxygen, sodium and calcium ions which are responsible in the activation of proteases and cell death. Heart renin angiotensin system (RAS) plays an important role in the myocardial ischemia and reperfusion injury. Angiotensin (1–7) is responsible for vasodilation and angiotensin II for vasoconstriction. Here-in we reviewed how myocardial I/R injury sets in by up-regulation of angiotensin II that leads to increased infarct size, which can be reduced by the use of ACE inhibitors, ACE2 activators and angiotensin II antagonist.

Instability and Sustainability Analysis of Mustard in Bhind (Madhya Pradesh) and Relationship with Factors of Production on Productivity

The oilseed crops play a crucial role in Indian agricultural economy. The oil content varies from 37 to 49 percent. Oil is utilized for human consumption, seeds as spices and cake as a cattle feed and manure. Mustard is also an important oilseed crop containing over 40 percent oil on a dry weight basis. Madhya Pradesh (MP) is the fourth major mustard producing the state in India followed by Gujarat and West Bengal, with a share of nearly 11 percent of the countrys total mustard production. In present study sustainable growth in the area, production and yield of mustard during the period under investigation for whole Madhya Pradesh. While Madhya Pradesh is found sustainable in the area, production and productivity as compared to Bhind district, which is a witness that Bhind district is having more fluctuation in the area, production and productivity of mustard during the study under investigation. Hence, in recent years a concept of sustainable agriculture is developed in order to ensure that the agro-eco-systems are stabilized and sustained crop yields are assured on a long term basis.

Involvement of atrial natriuretic peptide in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart

Background: Nitric oxide (NO) is an effective mediator of ischemic preconditioning (IPC)-induced cardioprotection. Atrial natriuretic peptide (ANP) is downregulated after ovariectomy, which results in reduction in the level of NO. The present study deals with the investigation of the role of ANP in abrogated cardioprotective effect of IPC in the ovariectomized rat heart. Methods: Heart was isolated from ovariectomized rat and mounted on Langendorff’s apparatus, subjected to 30 min of ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Krebs–Henseleit solution. The myocardial infract size was estimated employing triphenyltetrazolium chloride stain, and coronary effluent was analyzed for creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release to consider the degree of myocardial injury. The cardiac release of NO was estimated by measuring the level of nitrite in coronary effluent. Results: IPC-mediated cardioprotection was significantly attenuated in ovariectomized rat as compared to normal rat, which was restored by perfusion with ANP. However, this observed cardioprotection was significantly attenuated by perfusion with L-NAME, an endothelial nitric oxide synthase inhibitor, and Glibenclamide, a KATP channel blocker, alone or in combination noted in terms of increase in myocardial infract size, release of CK-MB and LDH, and also decrease in release of NO. Conclusion: Thus, it is suggested that ANP restores the attenuated cardioprotective effect of IPC in the ovariectomized rat heart which may be due to increase in the availability of NO and consequent increase activation of mitochondrial KATP channels.

Prodrugs of NSAIDs: A Review

Intoroduction: Prodrug approach deals with chemical biotransformation or enzymatic conversion or involves inactive or less active bio-reversible derivatives of active drug molecules. They have to pass through enzymatic or chemical biotransformation before eliciting their pharmacological action. Methods & Materials: The two different pharmacophores combine to give synergistic activity or may help in targeting the active drug to its target. Prodrug super seeds the problems of prodrug designing, for example solubility enhancement, bioavailability enhancement, chemical stability improvement, presystemic metabolism, site specific delivery, toxicity masking, improving patient acceptance, or eradicating undesirable adverse effects. Results: As an outcome the search for a prodrug or mutual prodrug with reduced toxicity has continued during recent years. This present review emphasizes the common help to revamp physiochemical, pharmaceutical and therapeutic effectiveness of drugs. Conclusion: This gives the researcher a common platform where they can find prodrugs of commonly used NSAIDs to overcome the gastrointestinal toxicity (irritation, ulcergenocity and bleeding).

Pharmacological screening of some newly synthesized triazoles for H 1 receptor antagonist activity

The present work deals with the pharmacological screening of some newly synthesized triazoles. A series of 1,2,4-triazoles have been synthesized using benzoic acid or 4-chloro benzoic acid as the starting materials. The synthesized compounds were characterized by physical and spectral analysis viz., Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, Gas Chromatography-Mass Spectrometry and elemental analysis Carbon, Hydrogen and Nitrogen analysis in order to confirm the structure. Acute toxicity studies were carried out in accordance with the Organization for Economic Co-operation and Development guideline 425. The compounds were not found to be lethal even at a dose level of 2000u2009mg/kg. Pharmacological evaluation was done following three intact animal experiments and one experiment on the isolated tissue. Results of the study indicated that the compound 7bi and 7bj protected up to 60% against histamine-induced dyspnea. Antihistaminic nature of the test compounds 7bi, 7bj, 7ai, and 7bk were also confirmed by the loss of catalepsy after the administration of clonidine (1%, s.c.). During experiments on isolated tissue, suppression of dose-response curve of histamine indicates a noteworthy denouement in favor of the said effect.

Antimicrobial Screening of Some Newly Synthesized Triazoles

The study deals with the synthesis and evaluation of some novel triazoles. Amine linked triazoles were prepared through multistep syntheses. 4-Iodobenzoic acid was taken as initial reactant material, which was converted into methyl ester, then to hydrazide and finally into triazole via dithiocarbazate salt. The triazole was treated with chloroacetyl chloride and further with secondary amines to get the title compounds. Structures of the synthesized compounds were elucidated by Fourier transform infrared spectroscopy (FTIR), 13C and 1H nuclear magnetic resonance (NMR), mass spectrometry and elemental analysis. The synthesized compounds were screened for their antimicrobial activity. The study was carried out against four bacteria and three fungi by disc diffusion method using ciprofloxacin and fluconazole as reference drug for antibacterial and antifungal activities respectively. All the synthesized compounds exhibited zones of inhibition against Candida albicans, Aspergillus niger and Fusarium oxysporum, but the inhibition was more prominent as shown by compound T83. Similarly antibacterial activity was studied against Staphylococcus aureus, Basillus subtilis, Psedomonas aeruginosa and Escherichia coli. Data revealed that compounds T81 and T83 were effective against the bacterial strains. Minimum inhibitory concentration test (MIC) was also carried out to ascertain the bacteriostatic property of the test compounds.

PREVALENCE AND RISK FACTOR OF POLYCYSTIC OVARIAN SYNDROME

ABSTRACT Various studies have already been performed involving the whole aerial parts of Centella asiatica (L.) (Umbelliferae), commonly known as gotu kola or jalbrahmi, and thus, the present investigation has been carried out for the phytochemical study of an ethanolic extract of the aerial parts of C. asiatica. To perform this activity, the drug (1.5 kg) was exhaustively extracted in 95% ethanol using Soxhlet apparatus. The column chromatography was performed then for isolating the various phytoconstituents using the solvents of increasing polarity from petroleum ether to methanol. The isolated compounds were structurally elucidated using various spectral data analysis, i.e. infrared,1H nuclear magnetic resonance (NMR),13C NMR, and positive ion fast atom bombardment mass spectrometry. One of the isolated compounds was characterized as n-heptacosanyl oleate. Keywords : Whole aerial parts, Centella asiatica, Soxhlet, Column, Heptacosanyl oleate.