Tryptanthrin from microwave-assisted reduction of isatin using solid-state-supported sodium borohydride: DFT calculations, molecular docking and evaluation of its analgesic and anti-inflammatory activity

Abstract

Tryptanthrin is a potent natural alkaloid with good in vitro pharmacological properties. Herein, we report the synthesis of the compound via a new method involving the reduction of isatin with solid-state-supported sodium borohydride under microwave irradiation. The title compound has been tested for its analgesic and antiinflammatory activity. The results showed that tryptanthrin dose dependently inhibits oedema and pain formation in all the models used. The agent also exhibited significant higher effects in its anti-inflammatory and analgesic activities better than positive drugs (aspirin and indomethacin) being currently used in the treatment and in the management of acute and chronic forms of pain and inflammatory disorders. The inhibitory potential of the compound was investigated by molecular docking using the software AutoDock Vina. The docking results were used to better rationalize the action and prediction of the binding affinity of tryptanthrin. Density Functional Theory (DFT) calculations at the B3LYP/6-311þþG (2df, 2pd) level of theory showed that compared to ascorbic acid, tryptanthrin shows higher antioxidant activity which may be improved upon by functionalizing the aromatic core to enhance its solubility in polar solvents. The calculated electronic and thermodynamic properties obtained for tryptanthrin compete well with the standard ascorbic acid.

Tryptanthrin and Its Derivatives in Drug Discovery: Synthetic Insights

“…The authors proposed a mechanism involving an initial ring-opening step via a hydrolysis of the 2-carbonyl unit to form 2-aminophenylglyoxylic acid, followed by condensation with a second isatin molecule, with loss of CO 2 , which further reacts via intramolecular cyclization to afford tryptanthrin in moderate yield (30%) (Scheme 3 ). 26…”

“…The authors proposed a mechanism involving an initial ring-opening step via a hydrolysis of the 2-carbonyl unit to form 2-aminophenylglyoxylic acid, fol-lowed by condensation with a second isatin molecule, with loss of CO 2 , which further reacts via intramolecular cyclization to afford tryptanthrin in moderate yield (30%) (Scheme 3). 26 Scheme 3 MW-assisted reduction of isatin to tryptanthrin using NaBH 4 /SiO 2 Using a different starting material, Zheng and co-workers explored the use of the oxidant (NH 4 ) 2 S 2 O 8 to promote C-H/N-H cross dehydrogenative coupling to attain several polycyclic quinazolinones, including tryptanthrin (34%). Mechanistically, the reaction seems to be reliant on the for-Scheme 1 Iodine-promoted approaches for tryptanthrin synthesis…”

Discovery and Mechanism of Azatryptanthrin Derivatives as Novel Anti-Phytopathogenic Bacterial Agents for Potent Bactericide Candidates

“…14 Tryptanthrin (Tryp) alkaloid, isolated mainly from indigo plants, such as Polygonum tinctorium, Strobilanthes cusia, and Isatis tinctoria, is also the main medicinal ingredient of Radix isatidis, a traditional Chinese medicine. 15,16 Tryp derivatives exhibit various biological activities, including antibacterial, 17 anti-inflammatory, 18 antileishmanial, 19 antiviral, 20 and antimalarial, 21 such as phaitanthrin A, phaitanthrin B, and some reported compounds with potential anticancer small molecule structure (Figure 1A). 22−24 Owing to the antibacterial activities of Tryp and its derivatives, we modified the basic skeleton of Tryp and introduced nitrogen heteroatoms into different positions in the A ring.…”

“…However, due to the limited resources of natural products, low content of active ingredients, insufficient activity, weak specificity of action, unreasonable pharmacokinetic properties, and other deficiencies, it is necessary to modify and optimize the structure of lead compounds by means of chemical synthesis to develop them into ideal drugs . Tryptanthrin (Tryp) alkaloid, isolated mainly from indigo plants, such as Polygonum tinctorium, Strobilanthes cusia, and Isatis tinctoria, is also the main medicinal ingredient of Radix isatidis, a traditional Chinese medicine. , Tryp derivatives exhibit various biological activities, including antibacterial, anti-inflammatory, antileishmanial, antiviral, and antimalarial, such as phaitanthrin A, phaitanthrin B, and some reported compounds with potential anticancer small molecule structure (Figure A). − …”

Design, synthesis, molecular modeling, and antimicrobial potential of novel 3‐[(1H‐pyrazol‐3‐yl)imino]indolin‐2‐one derivatives as DNA gyrase inhibitors

“…[22] On the other hand, 2,3-dioxoindole is an influential group of biologically active heterocyclic compounds and of considerable importance in medicinal chemistry. [23] The 2,3-dioxoindole (isatin) shows a broad range of biological activities such as anticonvulsant, [24,25] anti-inflammatory, [26] anticancer, [27] antibacterial (Figure 1), [28,29] antidepressant, [30] anti-HIV, [31] α-glucosidase inhibitors, [32] antitubercular agents, [33] and antileukemic activity. [34] Schiff bases have shown several biological activities such as anticancer, [35] antibacterial, [29,36] antifungal, [37] and biocidal activities.…”