Synthetic modifications of abietane diterpene acids to potent antimicrobial agents

Abstract

Among abietane type semisynthetic diterpenoids, a series of quinopimaric and maleopimaric acid derivatives modified at the carboxyl and carbonyl groups, and in ring E were synthesized to obtain new compounds with antimicrobial potency against Micobacterium tuberculosis H37Rv and key ESKAPE pathogens. It was found that dihydroquinopimaric N-{4'-[(3'-аminopropyl)amino]butyl} carboxamide (8) exhibited low toxicity to human embryonic kidney cell line HEK-293 (> 32 μg/mL) and showed significant bacteriostatic activity against methicillin-resistant Staphylococcus aureus (MRSA) (MIC ≤ 0.25 g/mL) and excellent antifungal activity against Cryptococcus neoformans var. grubii (MICs ≤0.25 g/mL) being 4 and 30 fold more active than vancomycin and fluconazole; it also showed moderate activity against fungi Candida albicans (MIC ≤ 0.25 g/mL). Methyl 1,4-bis(isonicotinoylhydrazono)dihydroquinopimarate (9) inhibited M. tuberculosis H37Rv with MIC of 1.25 µg/mL. The docking studies suggest possible interactions of the leading compounds with the molecular targets.

Uncovering a miltiradiene biosynthetic gene cluster in the Lamiaceae reveals a dynamic evolutionary trajectory

“…However, abietanes have been extensively studied for their importance to human health. They exhibit a range of bioactivities from anti-tumor to antimicrobial to anti-inflammatory, among others [60][61][62][63]101 . Nearly 500 abietane diterpenoids have been reported to date in Lamiaceae species 40,102 .…”

Bicyclic guanidine superbase carboxylate salts for cellulose dissolution

“… 30 On the other hand, spermidine ( N 1-(3-aminopropyl)butane-1,4-diamine) is well known, but usually used only in small quantities in mostly biological research, making it expensive. 31 A few other branched triamines are known, but available only in minor quantities. Therefore, we decided to explore possible pathways towards various triamines to allow for the facile synthesis of various bicyclic guanidines.…”

New Molecules of Diterpene Origin with Inhibitory Properties toward α-Glucosidase

“…For the synthesis of quinopimaric acid 1 [ 38 ] pine resin Pinus silvestris (containing about 25% levopimaric acid) was used. Compounds 2 , 14 , 15 , 17 – 21 , 24 [ 50 ], 3 [ 51 ], 4 [ 52 ], 5 [ 53 ], 6 , 9 , 11 , 26 – 28 , 30 [ 16 ], 7 [ 54 ], 8 [ 50 ], 10 [ 55 ], 12 , 13 [ 56 ], 16 [ 15 ], 22 , 23 [ 57 ], 25 [ 58 ], 29 [ 59 ], 31 , 32 , 34 [ 60 ], 33 [ 14 ], 35 [ 61 ], 36 – 39 [ 38 ], 40 , 49 [ 62 ] were obtained according to the methods previously described.…”

“…Abietane diterpenoids are classes of compounds which are mainly found in the conifer family and have long been used to treat a variety of ailments [ 13 ]. Their derivatives are characterized by a wide range of biological activities, like anticancer, antiviral, antimicrobial, antileishmanial, antiplasmodial, antifungal, antitumour, cytotoxicity, antiulcer, cardiovascular, antioxidant, anti-inflammatory and antidiabetic activities [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Abietic and dehydroabietic acids have been reported to decrease the activity of glucose-6-phosphatase and to stimulate glycogen synthase [ 22 ].…”