Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines

Abstract

Pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5-a]pyrimidines showed that the pyrazolo[1,5-a]pyrimidines (5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i confirmed that most of the compounds (i) were within the range set by Lipinski’s rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.

Copper-based glass-ceramic as an efficient catalyst in the synthesis of pyrazolo[1,5-a] pyrimidineunder solvent-free condition with docking validation as Covid-19 main protease (Mpro) inhibitor

“…In this special corona virus pandemic, M pro is considered as a valuable target and unique challenge. The active binding site is presented by Liu et al [40] and in the extension of our research group [41][42][43][44] to discover new efficient ligand-receptor interaction.…”

One‐potandtwo‐potmethods for chalcone derived pyrimidines synthesis and applications

“…[216] Another triazine based pyrimidine having 1,4-oxazine (75) has also been prepared from chalcone (73) with guanidine under basic media at 4-6 h reflux to form 49%-65% yield product. [217,218] The trifluoro substituent based pyrimidine (75) was conveniently synthesized using the same two-pot method [219] [215] whereas the substituent of 4-N-(CH 3 ) 2 C 6 H 4 showed excellent antituberculosis activity. [219] Pyrimidine, featuring coumarin moieties (78), has been synthesized from the guanidine hydrochloride reaction with coumarin chalcone (76) in acidic HCl under ethanol reflux to give 40%-68% yield.…”

“…[53,54] antifungal, [55,56] antiviral, [57][58][59] antibacterial, [60] antimalarial, [61] anti-HIV, [62,63] antiulcer, [64] insecticide, [65] antineoplastic, [66] antiepileptic, [67] analgesic, [68] and anthelmintic. [69] Several commercially available drugs derived from pyrimidine are sildenafil (viagra), formycin A, [70] sulfadiazine, [71] pyrimethamine, [72] roscovitine, [73] indiplon, zaleplon, [74] ocinaplon, [75] dinaciclib, [75] fluorastrol, [76] 5-fluorouracil, [77] ispinesib, [78] volasertib, [79] pictilisib, monastrol, [80] and etravirine [81] (Figure 2).…”

Antibacterial evaluation and molecular properties of pyrazolo[3,4-b] pyridines and thieno[2,3-b]pyridines

“…The physicochemical, pharmacokinetic, and druglikeness properties of pyrazolo [3,4-b]pyridines 6a-h and thieno[2,3-b]pyridines 8a-h were predicted using the SwissADME website (http://swissadme.ch) (Al-Wasidi et al, 2020;Elsherif et al, 2020;Naglah et al, 2020).…”