4-(2-chloroacetamido) Benzoic Acid Derivatives as Local Anesthetic Agents: Design, Synthesis, and Characterization

 

4-(2-chloroacetamido) Benzoic Acid Derivatives as Local Anesthetic Agents: Design, Synthesis, and Characterization

 Ashish A. Kanhed1, Ashok P. Mehere1, Kavita R. Pandey2, Debarshi Kar Mahapatra3*

1Department of Pharmaceutical Chemistry, Sharad Pawar College of Pharmacy, Nagpur – 440104, Maharashtra, India

2Department of Pharmaceutical Chemistry, Kamla Nehru College of Pharmacy, Nagpur – 441108, Maharashtra, India

3Department of Pharmaceutical Chemistry, Dadasaheb Balpande College of Pharmacy, Nagpur – 440037, Maharashtra, India

Abstract

Local anesthetic activity was investigated with an assumed hypothesis that the essential alkyl substituted nitrogen having strong ionization characteristics (pKa in basic side) generally found in local anesthetics can be replaced by amide nitrogen, having chloro methyl group attached to the carbonyl carbon of amide. In this type of arrangement, the inductive effect exerted by chlorine provided enough ionization character to amide nitrogen. Eight esters, ten amides and one imidazole derivatives of 4-(2-chloroacetamido) benzoic acid were synthesized by Fischer’s esterification, Schotten-Baumann and substitution reactions. The synthesized derivatives (A1–A18 and A.im) were characterized by various instrumental techniques.ACD Lab Suite® was used to determine various physiochemical properties of synthesized molecules. Initially, infiltration local anesthetic activity was determined by Bianchi’s method. Five compounds (A1, A2, A4, A10, and A.im) showed promising local anesthetic activity, where the comparison was made with lignocaine HCl, thus conforming assumed hypothesis. However, the studied compounds have potency lower than that of lignocaine HCl. Compounds showing promising activity with low toxicity were studied further by in-vivo rat sciatic nerve block method using increasing doses. A.im was studied for topological similarity with lignocaine HCl where it showed good local anesthetic activity and was relatively very less toxicity. The reduced toxicity of these molecules may be attributed due to the carbonyl chloro methyl side chain. Further structural advancement may be done by researchers to increase the potency of these compounds since they are relatively less toxic than lignocaine.

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Aqueous Ethanol Fruit Extract of Xylopia aethiopica and Xylopic Acid Exhibit Anti-inflammatory Activity Through Inhibition of the Arachidonic Acid Pathway

 

Newman Osafo1*, Robert P. Biney1,2, David D. Obiri1

1Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of  Science and Technology, Kumasi, Ghana

2Department of Pharmacology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana

Abstract

In the form of a decoction, X. aethiopica is traditionally employed in the treatment of bronchitis, asthma, arthritis and rheumatism in Ghana, Nigeria and Cameroon. This study establishes the inhibitory effect of X. aethiopica and its principal constituent, xylopic acid, on the arachidonic acid pathway of inflammation.Hydrogen sulphide is endogenously produced in mammalian tissues from the enzymatic activity of cystathionine β-synthase and cystathionine γ-lyase on L-cysteine. Its involvement in the local and systemic inflammatory process has been documented in animal models. Recent studies have identified its activation of phospholipase A2 as the mechanism involved in its anti-inflammatory role. We henceforth conducted this study to investigate the inhibitory role of X. aethiopica and its principal constituent xylopic acid on hydrogen sulphide-induced inflammation and eventual effect on the activation of phospholipase A2.Sodium hydrogen sulphide (NaHS) was injected into the mouse hind paw and oedema was monitored for 60 min. Paws were examined by the histological method.X. aethiopica extract (30, 100, 300 mg kg-1) suppressed the mean maximal swelling attained at 15 min to 42.58±1.66%, 42.58±1.66% and 34.91±2.39%, respectively compared to the mean inflamed control response of 61.51±3.90%. The total paw swellings induced over the 1 h were also significantly suppressed by 31.82±5.28%, 36.19±6.01%, and 31.65±5.16%, respectively. The xylopic acid (10, 30, 100 mg kg-1) suppressed the mean maximal swelling attained at 15 min to 41.75±1.24%, 40.26±1.68% and 38.26±2.52%, respectively relative to the control response while the total paw swelling was significantly suppressed by 34.08±4.49%, 38.19±4.50% and 43.40±5.09% respectively relative to the inflamed control response. Histologically, there was a significant (P < 0.0001) reduction in cytoplasmic vacuolation, inflammation, cellular degeneration, loss of tissue organisation and necrotic tissues with administration of X. aethiopica extract and xylopic acid in the inflamed paws of the mice. This study establishes that X. aethiopica extract, and xylopic acid mediate their anti-inflammatory actions in part through inhibition of hydrogen sulphide-induced inflammation and subsequently has an inhibitory role on phospholipase A2 activation.

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Effect of Natural Honey on Intestinal Transit in Rats

 

E. A. Alagwu , E. E. Ngwu , D. N. Alagwu , G. C. Uloneme*

Departments of Physiology and Anatomy, College of Medicine, Imo State University, Owerri- 460222, Nigeria

Abstract

Honey is a natural sweet substance produced by honey bees. Honey has a very complex chemical composition that varies depending on the botanical source. It has been used both as food and medicine since ancient times. Honey has long been used for treatment of various diseases in folk medicine around the world. The present study was planned to explore the effect of Natural Honey (NH) on the intestinal transit of rats. The rats were fed chow, fresh palm oil diet (FPOD), Thermoxidized Palm Oil Diet (TPOD) and NH; and further the transit point was calculated as a percentage of the total length of the intestine. The NH treated rats significantly decreased the intestinal transit of rats compared to other groups.  The findings exhibited that natural honey used for the treatment of diarrhoea. 

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Estimation of Total Flavonoids and Antioxidant Activity of Spilanthes acmella Leaves 

 

Nelofar Gulam Nabi*, Mukta Shrivastava 

Govt. Maharani Laxmi Bai Girls` P.G. (Autonomous) College, Bhopal (M.P.)-462002, India

Abstract

Flavonoids are a group of polyphenolic compounds, which are widely distributed throughout the plant kingdom. Flavonoids of different classes exhibited various pharmacological and biological activities. The present study was undertaken to investigate the total flavonoids and antioxidant effect of Spilanthes acmella leaves. The ethanol extract of Spilanthes acmella leaves were prepared and performed its phytochemical screening. The total flavonoids and polyphenol were investigated to quantify the presence of polyphenol compounds. The 2,2-diphenyl-1-picryl-hydrazil stable radical (DPPH) and Superoxide scavenging radical were used to determine extract antioxidant activity. The concentrations of flavonoids polyphenol in ethanol extract of Spilanthes acmella were 72.14 QE mg/gm and 84.52 GAE mg/gm, respectively.  The extract exhibited the strongest antioxidant activity, with the lowest IC50 ­value for DPPH and Superoxide scavenging. The IC50 ­value for DPPH and Superoxide scavenging were 134.11 µg/ml and 104.51 µg/ml, respectively.   The strongest antioxidant activity of ethanol extract could be due to the presence of flavonoids and phenols. 

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