Ravinesh Mishra

Benzimidazole clubbed with triazolo-thiadiazoles and triazolo-thiadiazines: New anticancer agents

Two series of Benzimidazole clubbed with triazolo-thiadiazoles (5a-q, 5r, 5s and 5x-a(1)) and triazolo-thiadiazines (5t-w) were synthesized with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were investigated at the National Cancer Institute (NCI) against NCI 60 cell line panel; results showed good to remarkable broad-spectrum anticancer activity. Among them, the compound 5h (NCS: 760452, 1-(1H-benzo [d] imidazol-2-yl)-3-(6-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl) propan-1-one) exhibited significant growth inhibition with GI50 values ranging from 0.20 to 2.58 μM and found superior selectivity for the leukemia cell lines and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). The 5h may possibly be used as lead compound for developing new anticancer agents.

Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents

Starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (1), twenty new 1-(1H-benzo[d]imidazol-2-yl)-3-(1,3,4-oxadiazol-5-substituted derivatives-2-yl)propan-1-ones (1b-A(7)(-)(26)) were synthesized under microwave irradiation in good yields. Further, compound 1b-A(7) was reacted with different secondary amines under microwave irradiation to produce five novel 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(methyl substituted)-1,3,4-oxadiazol-2-yl)propan-1-ones (1b-A(7a)(-)(e)). The title compounds were screened for their in vitro anticancer activity at National Cancer Institute (NCI), USA; at a single dose (10 μM) in NCI 60 cell line panel and results showed significant to good anticancer activity. One compound, 1b-A(18) (NSC: 759205), 1-(1H-benzo[d]imidazol-2-yl)-3-(5-(2,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl)propan-1-one, emerged as lead compound; it was selected for five-dose level screening and found to have significant growth inhibition activity.

Synthesis, characterization and antihypertensive activity of pyridazinone derivatives

Some 6-(substituted-phenyl)-2-(substitutedmethyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by reacting 6-substituted-phenyl-4,5-dihydropyridazin-3(2H)-one with cyclic secondary amine under Mannich reaction conditions. The final compounds (15-70) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 16, 19, 24, 30, 39, 42 and 45 showed good antihypertensive activity.

Benzimidazole bearing oxadiazole and triazolo-thiadiazoles nucleus: Design and synthesis as anticancer agents

Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a-l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a-e)] have been synthesized successfully from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM) with GI(50) values ranging from 0.49 to 48.0 μM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI(50) 0.49, TGI 19.9,LC(50) >100 and Log(10)GI(50) -6.30, Log(10)TGI -4.70, Log(10)LC(50) >-4.00).

Triazole incorporated pyridazinones as a new class of antihypertensive agents: Design, synthesis and in vivo screening

A number of 6-(substituted phenyl)-2-(4-substituted phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were designed and synthesized by a sequence of reactions starting from respective aryl hydrocarbons. The final compounds (4a-4u) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 4e, 4i and 4k showed appreciable antihypertensive activity comparable with that of standard hydralazine and propranolol.

Analytical methods for the detection of undeclared synthetic drugs in traditional herbal medicines as adulterants.

Traditional herbal medicines (THMs) are gaining popularity worldwide as an alternative approach to prescription drugs for many reasons including a general perception that they are safe. But recently there have been number of reported studies that reveal adulteration of THMs with undeclared synthetic drugs, which may potentially cause serious toxic adverse effects. This paper reviews the various classes of synthetic drugs that were found to be adulterated in THMs worldwide. The main focus is to highlight newer analytical tools used to detect adulteration. Due to the advancement in hyphenated techniques like liquid chromatography tandem mass spectrometry (LC-MS/MS), gas chromatography-tandem mass spectrometry (GC-MS/MS) and other conventional tools, it has become possible to detect synthetic drugs and their structural analogues as adulterants even if they are present in small quantities. This review also gives an overview of health-related risks after consuming such spurious products and challenges for future perspectives to control such type of malpractices.

Application of LC–MS/MS for quantitative analysis of glucocorticoids and stimulants in biological fluids

Liquid chromatography tandem mass chromatography (LC–MS/MS) is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC–MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches (column packing materials, column length and mobile phase) as well as different acquisition modes (SIM, MRM) for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC–MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.

SYNTHESIS AND In vitro ANTIMICROBIAL ACTIVITY OF SOME TRIAZOLE DERIVATIVES

Some 4-[{1-(substituted)methylidine}-amino]-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazol (3a- 3f) and N-[5-(4-substituted)-1H-1,2,3-triazol-1-yl]isonicotinamide derivatives (5a- 5e) were synthesized by a sequence of reactions starting from isonicotinic acid hydrazide and is illustrated in scheme 1 and 2. The antibacterial and antifungal activities of newly synthesized compounds were tested by the disc diffusion method using nutrient agar medium against various microorganisms such as gram positive Staphylococcus aureus and Bacillus subtilis, gram negative Escherichia coli and the fungi Aspergillus niger and Candida albicans. Ciprofloxacin and Fluconazole at 50 μg/mL were used as standard drugs for antibacterial and antifungal activities, respectively. All the synthesized compounds showed significant activity against various microorganisms.

1-(1H-Benzimidazol-2-yl)-3-[5-(trichloromethyl)-1,3,4-oxadiazol-2-yl]propan-1-one

The title compound, 1-(1H-benzimidazol-2-yl)-3-[5-(trichloromethyl)-1,3,4-oxadiazol-2-yl]propan-1-one (2) was synthesized successfully from 4-(1H-benzimidazol-2-yl)-4-oxobutanehydrazide (1) under microwave irradiation in good yield by reacting with trichloroacetic acid, and the structure of title compound was confirmed on the basis of IR, 1H-NMR, 13C-NMR, MS and CHN analyses results.

Synthesis, spectral characterization, and pharmacological screening of some 4-[{1-(aryl)methylidene}-amino]-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazole derivatives

Background: Pain is an unpleasant and subjective sensation that results from a harmful sensorial stimulation, which alerts the body about current or potential damage to its tissues and organs. Fever is a complex physiological response triggered by infections or aseptic stimuli. Elevation in body temperature occurs when the concentration of prostaglandin E2 (PGE2) increases within parts of the brain. Triazole derivatives have been found to possess various pharmacological and biological activities, such as, anti-inflammatory, analgesics, antipyretic, and antifungal. Materials and Methods: Various 4-[{1-(aryl)methylidene}-amino]-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazole derivatives were synthesized by a sequence of reactions starting from isonicotinic acid hydrazide. The synthesized compounds were screened for in-vivo analgesic by the tail-flick method and anti-pyretic activities at a dose of 25 and 100 mg/kg body weight respectively. The antipyretic activity was evaluated using Brewers yeast induced pyrexia in rats. Fever was induced by subcutaneously injecting 20 ml/kg of 20% aqueous suspension of Brewers yeast in normal saline. Results and Discussion: The analgesic screening results revealed that the compounds 3b, 3c, and 3d exhibited excellent analgesic activity at 60 and 90 minutes compared to the standard drug (Analgin). Results revealed that the compounds 3a, 3e, and 3f significantly decreased the temperature of pyretic (P<0.001) rats at one, three and six hours after compound administration as compared to Aspirin (standard drug). Conclusion: Compounds 3b, 3c, and 3d exhibited significant analgesic activity comparable with the standard drug analgin, using the tail flick model. Compounds 3a, 3e, and 3f showed significant anti-pyretic activities comparable with the standard drug aspirin using the yeast-induced pyrexia model.