2018 Springer Science+Business Media, LLC
Chemistry of Natural Compounds, Vol. 54, No. 3, May, 2018
IMPROVED SYNTHESIS OF DBIBB AS A NEW ANTI-RADIATION AGENT
and Lin Wang
An excellent candidate in the fight against damage caused by nuclear radiation is 2-[4-(1,3-dioxo-1H,3H-
benzoisoquinolin-2-yl)butylsulfamoyl]benzoic acid (DBIBB), a lipid agonist of lysophospholipid acid receptor
2. In this study, a novel method that synthesizes DBIBB was developed. In this method, saccharin was
replaced singly by 1,4-dibromobutane, reacted with 1,8-naphthalimide, hydrolyzed by sodium hydroxide,
and finally acidified by hydrochloric acid to obtain DBIBB. The new synthesis route was shorter, milder, and
simpler than previously reported approaches. The method also produced higher total yield than that of
existing ones. Thus, it is applicable to the large-scale synthesis of DBIBB.
Keywords: DBIBB, lysophospholipid acid receptor 2, saccharin, new method.
Almost 70 years into the nuclear age, mitigation of injuries caused by exposure to high levels of ionizing radiation has
become a challenge; such radiation induces DNA strand breaks, which occurred during the Tokaimura, Fukushima, and Chernobyl
nuclear plant disasters or during the explosion of a nuclear device. Although cells can repair the damage, serious damages may
lead to cell death within a few weeks . The DNA damage caused by ionizing radiation must be effectively repaired to allow
cell cycle progression and avoid oncogenic or lethal mutations and aberrant chromosomes that could lead to mitotic catastrophe.
Lysophospholipid acid (LPA), a potent antiapoptotic agent for intestinal epithelium, promotes cell damage repair .
LPA is a kind of lecithin with the simplest structure. It is a key precursor in the early phase of biosynthesis of
eukaryotic cell phospholipids and the intermediate product of glycerol phospholipid metabolism. LPA, as a kind of phospholipid
messenger between cells, can has a growth-hormone-like effect, resulting in a wide range of biological effects. LPA also has
various effects on cell growth, proliferation, differentiation, and cell information and is crucial in maintaining the bodycs
normal physiology in the development of various pathological processes. In addition, LPA can inhibit cell apoptosis after
radiation injury [3, 4]. Lysophospholipid acid receptor 2 (LPA
receptor) is a G protein coupled receptor. The lipid agonist
receptor is an important basis of protection from radiation damage and treatment of acute radiation sickness. American scientists
have developed a specific LPA
receptor agonist by using a computer model. Furthermore, 2-[4-(1,3-dioxo-1H,3H-
benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid (DBIBB) is an ideal treatment agent when administered in high doses
(15.69 gray) for acute radiation sickness, particularly with delayed healing. DBIBB mitigates radiation-induced apoptosis and
crypt loss and augments cell proliferation. This molecule can also protect mice embryonic skin cells from DNA damage
induced by radiation and improve the survival rate of blood and intestinal cells exposed to radiation. DBIBB also represents
the first radiomitigator small molecular drug candidate for reducing mortality caused by hematopoietic and gastrointestinal
acute radiation syndromes [5–7]. DBIBB can protect cells from radiation injury and enhance DNA repair via LPA
. It mitigates
cell and tissue injury in vitro and in vivo when used days after exposure to high levels of ionizing radiation; therefore, DBIBB
is an effective radiomitigator .
1) Anhui Medical University, 81 Mei Shan Road, 230032, Hefei, P. R. China, e-mail: email@example.com;
firstname.lastname@example.org; 2) Institute of Radiation Medicine, Academy of Military Medical Sciences, 27 Tai Ping Road, 100850,
Beijing, P. R. China, e-mail: email@example.com. Published in Khimiya Prirodnykh Soedinenii, No. 3, May–June, 2018,
pp. 423–425. Original article submitted October 19, 2016.