Physiologic Activity of Bisphosphonates – Recent Advances

Abstract

Abstract:Background:

Synthetic Procedures Leading towards Aminobisphosphonates

“…Bisphosphonates are known for their affinity to bone tissue, and thus their conjugation to various drugs has been quite intensively studied; they are expected to serve as system-targeting drugs [6]. Because dronic acids are produced at industrial scale and are thus readily available and inexpensive, they are most frequently used for that purpose.…”

“…Most papers concern their important subclass, namely aminobisphosphonates. This strong interest results from these compounds acting as strong inhibitors of bone resorption, with several representatives of this class already commercialized as drugs of choice for the treatment of osteoporosis, skeletal complications of malignancy, Paget's disease, multiple myeloma, hypercalcemia and fibrous dysplasia [2][3][4][5][6][7] Consequently, most of the papers are devoted to various clinical aspects of the anti-resorptive effects that bisphosphonates exert towards bone tissues; however, there is also a growing interest in their applications as anticancer and antibacterial agents [5][6][7]. Additionally, aminobisphosphonic acids have found important industrial applications, largely as inhibitors of scale formation and as corrosion inhibitors, actions which result from their ability to complex metal ions [8][9][10].…”

Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products

“…Although the synthesis of bisphosphonic acids was described as early as the 19th century, the interest in these compounds is still growing, rooted in their promising and variable physiological activities [1]. Most commonly, their regulation of bone growth has been exploited for the design and preparation of antiosteoporotic drugs that can also be used to treat skeletal complications of…”

“…However, studies of sheep with induced osteoporosis carried out with compound trans-7 did not support this assumption.Molecules 2020, 25, 1424 2 of 18 various provenances [1][2][3][4]. These compounds also exert an inhibitory activity towards important medicinal enzymes, including farnesyl pyrophosphate synthase (thus inhibiting Ras farnesylation, as their structure makes them potential anti-cancer and/or anti-protozoan agents), glutamine synthetase (possible anti-tuberculosis agents), and undecaprenyl diphosphate synthase (antibacterials) [1,[5][6][7][8][9].Some patients who received intravenous and oral forms of bisphosphonate therapy for various bone-related conditions suffer osteonecrosis of the jaw, dependent on the dose and duration of the therapy [10]. The mechanism by which bisphosphonates might contribute to the development of osteonecrosis of the jaw is not well understood [11].…”

“…Molecules 2020, 25, 1424 2 of 18 various provenances [1][2][3][4]. These compounds also exert an inhibitory activity towards important medicinal enzymes, including farnesyl pyrophosphate synthase (thus inhibiting Ras farnesylation, as their structure makes them potential anti-cancer and/or anti-protozoan agents), glutamine synthetase (possible anti-tuberculosis agents), and undecaprenyl diphosphate synthase (antibacterials) [1,[5][6][7][8][9].…”