Gita Chawla

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study.

Syntheses and evaluation of anti-inflammatory, analgesic and ulcerogenic activities of 1,3,4-oxadiazole and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives

Several 2,5-disubstituted-1,3,4-oxadiazoles (4a–f) and 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (7a–f) were synthesized and characterized by elemental analyses and spectral data. These compounds were screened for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities. Compound 7c showed excellent anti-inflammatory and remarkable analgesic activity with reduced ulcerogenic and lipid peroxidation activity when compared with ibuprofen.

Synthesis and neuropharmacological evaluation of some new isoxazoline derivatives as antidepressant and anti-anxiety agents

A series of 3-(furan-2-yl)-5-(substituted phenyl)-4,5-dihydro-1,2-oxazole derivatives (2a to j) were synthesized by Claisen Schmidt condensation of 2-acetyl furan with different types of aromatic aldehyde, as chalcones and their subsequent cyclization to 4,5-dihydro-1,2-oxazole with hydroxylamine hydrochloride. The chemical structures of the synthesized compounds were confirmed by IR, 13 C-NMR and mass spectrometric data. This study further involves evaluation of synthesized compounds for antidepressant and antianxiety activities using force swimming test (FST) and elevated plus maze method, respectively. Most of the tested compounds were found to be moderate to significant activities at the dose level of 10 mg/kg, compared to reference drugs imipramine and diazepam, respectively. Compound 4-(3-(furan-2-yl)-4,5-dihydro-1,2-oxazol-5-yl)phenol (2e) emerged as the most potent antidepressant agent acting through monoamine oxidase (MAO) inhibition without any significant neurotoxicity. The molecular docking study were also carried out on the falcipain-2 receptor (PDB id: 2Z5X) for all the compounds and compound 2e was found to occupy in the receptor cavity and forms hydrogen bond and hydrophobic interactions with active residues.

Principle, Instrumentation, and Applications of UPLC: A Novel Technique of Liquid Chromatography

The key focus of the pharmaceutical or chemical industries is to reduce the cost involved in the development of new drugs and to improve the selectivity, sensitivity, and resolution for their detection. The purpose can now be solved by the separation method called UPLC which is the modified HPLC method comprising high pressure and small sized particles (less than 2 µm) used in the column, so the length of the column decreases leading to time saving and reduction in the consumption of solvent. The underlying principle of UPLC is based on van Deemter statement which describes the connection between linear velocity with plate height. UPLC contributes to the improvement of the three areas: speed, resolution, and sensitivity. This is a new advanced category of the HPLC which has the same basic principle and methodology with improved chromatographic performance. This review is an effort to compile the principle, instrumentation, and applications of UPLC.

Pyrazole incorporated 1,2-diazanaphthalene derivatives: Synthesis and in-vivo pharmacological screening as anti-inflammatory and analgesic agents

In the present study, a new series of compounds (3 to 22) containing pyrazole moiety clubbed with 1,2diazanaphthalene ring, structurally related to celecoxib and naproxen was synthesized. The compounds were evaluated for anti-inflammatory activity using carrageenan induced rat paw edema bioassay. Compounds showing marked anti-inflammatory activity were further tested for their analgesic, ulcerogenic and lipid peroxidation effect using naproxen as reference drug. The results showed that compounds 6, 13 and 14 exhibited good anti-inflammatory and analgesic activity with minimum gastric irritation. Compounds 13 and 14 emerged as potent anti-inflammatory (with percentage inhibition of 79.23 and 76) and analgesic agent (with percentage protection of 68.72 and 67.68) in the present study.

Chemical Modifications of Ketoprofen (NSAID) in Search of Better Lead Compounds: A Review of Literature From 2004-2016

BACKGROUND Ketoprofen, a potent anti-inflammatory, analgesic and anti-pyretic drug belonging to the propionic acid class was synthesized in 1968. Rapid absorption, simple metabolism, faster blood brain barrier crossing and high antinociceptive activity are the features responsible for its high use. But, free acidic moiety present in its structure is the major factor that declines its popularity by causing various gastric side effects. Many researchers have chemically modified this drug with the aim to discover an improved and safe NSAID candidate or a new drug with altered activity. We thoroughly searched the literature and found that during the period 2004-2016, more than fifty reports are available on chemical modification of ketoprofen. Along with this, many patents involving chemical modification of ketoprofen have also been reported. However, it was very surprising to note that there are only a few review articles available covering only its pharmacological and clinical properties. There is no review article available covering the chemistry part of ketoprofen. This motivated us to compile the information available on ketoprofen and its derivatives. The purpose of this article is to present an updated review about this topic. METHODS We thoroughly searched the peer reviewed research literature and compiled all such reportings (2004 onwards) for the benefit of researchers who further want to work on ketoprofen or other NSAIDs. RESULTS Studies have been conducted to invent strategies to reduce the ulcerogenic properties of ketoprofen and in the course of time, its modified and improved derivatives have been synthesized in search of safer NSAIDs. Along with the aim of reducing the gastric side-effects, researchers have also done chemical modifications in the structure of ketoprofen to improve its solubility, to alter its blood brain-barrierr permeability, to improve its pharmacodynamic profile and to get derivatives possessing antioxidant, antiviral, anticancer and immunomodulatory activities. CONCLUSION The findings of the review confirm that chemical modifications of ketoprofen decrease ulcer producing side effect while maintaining its desirable actions. Some derivatives were also found to possess better activity profile compared to the parent drug.

Design and syntheses of some new quinoxaline derivatives containing pyrazoline residue as potential antimicrobial agents

A series of 3-[{5-(substituted-phenyl)-3-(phenyl/4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl}carbonyl]quinoxalin-2-ol derivatives (3–24) were synthesized by reacting 2-hydroxy quinoxaline-3-hydrazide with different substituted 1,3-diphenyl prop-2-en-1-ones in absolute ethanol. The structures of all the compounds were established on the basis of spectral data (IR, 1H NMR 13C NMR, and mass) and elemental analysis. All the newly synthesized compounds were examined for their in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli, Penicillium citrinum, and Aspergillus niger by the agar-well diffusion method employing ofloxacin and ketoconazole as reference drugs. All the tested compounds were found to possess substantial antimicrobial activity. Compound 5 and 12 showed excellent antibacterial and antifungal activity against all the tested strains. It was interesting and encouraging to note that all the compounds established high-antifungal activity than standard drug ketoconazole against P. citrinum.

(8-Chloro-3-methyl-1H-pyrazolo(4,3-c)cinnolin-1-yl) (pyridin-4-yl)methanone

Abstract: ( 8-Chloro-3-methyl-1 H -pyrazolo[4,3- c ]cinnolin-1-yl) (pyridin-4-yl)methanone 2 has been synthesized through condensation of 3-acetyl-6-chloro-1 H -cinnolin-4-one 1 with isonicotinic acid hydrazide (INH) in absolute ethanol. The structure of the title compound 2 was established on the basis of IR, 1 H-NMR, 13 C-NMR and mass spectral data. Keywords: cinnoline; pyrazole; isonicotinic acid hydrazide Cinnoline is a benzfused pyridazine containing two nitrogen atoms at 1,2-position and it is categorized under benzfused diazines class of heterocyclic compounds. Literature shows several compounds containing a cinnoline moiety with a wide spectrum of pharmacological activities, like antimicrobial, anti-inflammatory, anticancer, antimalarial and antipsychotic etc. [1–5]. As a part of research on benzfused heterocyclic compounds [6], we report here the synthesis of ( 8-chloro-3-methyl-1 H -pyrazolo[4,3- c ]cinnolin-1-yl) (pyridin-4-yl)methanone

Exploring 1,3,4-Oxadiazole Scaffold for Anti-inflammatory and Analgesic Activities: A Review of Literature From 2005-2016

1,3,4-Oxadiazole derivatives are found to have a wide range of pharmacological activities and attracting the researchers to work on this nucleus. Literature survey indicates that many 1,3,4- oxadiazoles have been synthesized with the aim to get compounds of significant anti-inflammatory and analgesic activities with reduced adverse effects. The purpose of this review is to compile the reports on 1,3,4-oxadiazole derivatives possessing anti-inflammatory and analgesic activities. The review also includes the reports on 1,3,4-oxadiazole derivatives of existing NSAIDs in the last ten years.

Design, syntheses, characterization, and evaluation of 2-substituted-1,3-bis(1-naphthylmethyl)-imidazolidine derivatives in search of safer nonsteroidal anti-inflammatory drugs

Background: 1,2,3-trisubstituted imidazolidines are reported to have better anti-inflammatory activity than the reference drug indomethacin. Similarly, naphthalene nucleus plays a significant role in the drug design. Nabumetone and naproxen are naphthalene nucleus containing anti-inflammatory drugs available in the market. There are also reports that compounds having two naphthalene rings incorporated with a heterocyclic nucleus have good medicinal value. Based on these reports it was planned to synthesize hybrid compounds containing two naphthalene rings with imidazolidine nucleus. Aim: To obtain potent compounds having anti-inflammatory and analgesic activities with reduced gastrointestinal side effects. Materials and Methods: The reaction scheme includes the reaction between 1-naphthaldehyde with ethylenediamine to obtain diSchiff′s base (1) Reduction of this diSchiff′s base with NaBH 4 gave tetrahydrodiSchiff′s base (2) Further cyclization of 2 with appropriate aldehyde in the presence of ethanol formed 2-substituted-1,3-bis(1-naphthylmethyl)-imidazolidine derivatives (3a-n). The structures of these compounds were established on the basis of spectral data. All these compounds were tested for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation activities. Results and Discussion: The tested compounds (3a-n) showed anti-inflammatory activity ranging between 27.61% and 53.43%. The compound 3h showed the highest activity of 53.43% and 3n showed 53.02% inhibition at 20 mg/kg dose in rats compared with the standard drug indomethacin which showed 61.45% inhibition at the same dose. It was encouraging to note that both the compounds showed reduced ulcerogenic activity (less than half) compared to the standard drug indomethacin.