Antihypertensive activity, toxicity and molecular docking study of newly synthesized xanthon derivatives (xanthonoxypropanolamine)

Abstract

Context Xanthone derivatives have been reported to possess a wide range of biological properties. In effort to search new effective antihypertensive compounds, we have synthesizednovel xanthone derivatives (xanthonoxypropanolamines) and got patent for these compounds (The Patent Office, Government of India, S. No.: 011–016308, Patent No.: 250538). Objective In the present work, we attempted to establish the antihypertensive activity, toxicity and molecular docking study forthese newly synthesized compounds (1a, 1b and 2). Materials and method The preliminary antihypertensive screening was performed by administering synthesized compounds and standard drugs intraperitonially and orally into wistar rats. The change in systolic, diastolic and the mean blood pressure before and after the treatment of the drugs was measured on a Digital LE-S100 Blood Pressure Meter by Tail-cuff method non-invasively. Toxicity studies were carried out after oral administration of synthesized compounds to rats at doses of 25, 50, and 100mg/kg. The serum samples were tested for different toxicity parameters such as liver function test, kidney function test etc. The docking simulations of all the compounds were performed using Maestro, version 9.4 implemented from Schrodinger software suite. Results and discussion The result showed that the compound 1a, 1b and 2 have greater antihypertensive activity with almost equal or less toxicity profile in comparison to standard drug Propranolol and Atenolol. The docking score for the compound 1b was found -9.1 while for compound 1a and 2 were found -8.7 and -8.6 respectively. Conclusion These novel compounds i.e. 1a, 1b, and 2 have greater antihypertensive activity in comparison to standard drugs Propranolol and Atenolol. All these compounds do not have any toxicity.

Potential Combination of Xanthone Compounds from Mangosteen Fruit (Garcinia mangostana) with Eugenol Compounds in Basic Leaf (Ocimum sanctum) as Alternative Therapy in Preeclampsia

“…See Figure 1 for the process of search results. The 10 selected studies were consisted of 9 experimental studies and 2 randomized controlled clinical trial conducted in different countries such as Indonesia [8,11], Brazil [2,5], India [1,4,9], USA [3,6,10], Poland [7].…”

“…Five experimental studies and one RCTs resulted that mangosteen, especially xanthone, has a potential antihypertensive activity. 5,6,7,9,11 One experimental study resulted that mangosteen has a potential antihypertensive activity in pregnant women. 8 Two experimental studies and One RCTs resulted from eugenol has a possible antihypertensive activity.…”

Recent advances in the synthesis of xanthones and azaxanthones

“…The classical Grover, Shah and Shah method 95,96 constitutes a suitable approach for the synthesis of hydroxyxanthones from easily available salicylic acid derivatives and phenols heated along with zinc chloride in phosphoryl chloride. 33,39,43,49,51,60,65,[97][98][99][100][101][102][103][104] For the reaction to proceed directly to the desired xanthone, the 2,2′-dihydroxybenzophenone intermediate must contain an additional hydroxyl moiety ortho to the carbonyl group. Usually phloroglucinol is used in order to overcome this limitation; however, when other phenol derivatives like resorcinol are used, the synthetic pathway stops at the benzophenone form.…”

“…89,[206][207][208][209][210][211][212][213][214][215][216][217][218] 7 Diversification on the xanthone core Hydroxyl groups are undoubtedly one of the most versatile functional groups when it comes to structural modifications (Scheme 26). A myriad of examples have been described in the literature, including the reaction with alkyl halides for the transformation into alkoxy, 43,59,69,[219][220][221][222][223] haloalkoxy, 18,51,69,99,224 methyl alkyl-or aryl-piperazine moieties, 225 epoxypropanoxy 65,103,[220][221][222] oxirane 221 , oxypropanolamines, 103 benzenesulfonamides, 226 and propargyloxy. 45,52,54,63,106,118,173,227,228 When reacted with other compounds that are not alkyl halides, several other functional-Scheme 25 Other methodologies for the synthesis of xanthones.…”

Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats

“…Xanthones are polyphenolic compounds, and their structures are recognized for their importance in discovering new active compounds [ 20 ]. Indeed, several biological activities have been described for xanthones, including anti-inflammatory, antioxidant [ 21 ], cardioprotective [ 22 ], diuretic [ 17 , 23 ], and renal protective [ 24 ] effects.…”