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Background: REM sleep behavior disorder (RBD) is manifested by abnormal motor behavior with an endurance of tone during REM sleep. Studies suggest that patients taking Selective serotonin reuptake inhibitors (SSRIs) are at greater risk of developing REM sleep behavior disorder. Case Presentation: We present a case of 39-year-old female with a past medical history of spinal cord injury from a gunshot wound 19 years ago resulting in paraplegia, posttraumatic stress disorder(PTSD), chronic pain, and chronic sleep problem. After sertraline started and up-titrated to 200 mg for her anxiety, she noticed worsening of her nighttime sleep behavior. Her mother also witnessed sleepwalking episode and doing things which the patient had no recollection in the morning, including trying to take a bath and eat from the refrigerator. On her follow-up appointment, her sertraline was discontinued altogether and she was started on Escitalopram 5 mg. She tolerated the medication well, it helped moderately with her anxiety and by the time of this case report (approximately 1 month) patient did not report any sleep-related behavior. Conclusion: Since antidepressant medication is very commonly prescribed, it is important to be cautious of physiologic changes they may induce, even if the clinical significance of these changes is not fully elucidated. In addition, RBD may predict neurodegenerative disorders a couple of years earlier, so it may be used as an effective early marker of neurodegenerative diseases.

Helicid is a specific Chinese natural drug. Helicid, its congeners, and its derivatives exhibit pronounced biological activities, among which its hypnotic effects stand out. The well-documented sedation and analgesic activity and low side effects of helicid have drawn more and more attention from scientists. Moreover, its clinical success and intriguing mechanism of action have stimulated great interest in further modification of helicid for improving its hypnotic activity. The 4-formyl group has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug disadvantages. Accordingly, numerous helicid derivatives have been prepared via molecular docking and hemisynthesis. Although neither systematic nor comprehensive, there are two excellent reviews on the distribution, sources, applications, synthesis, and pharmacological activity of helicid that have been published in Chinese. In the present review, we attempt to compile and discuss the key data available in the literature on the multiple biological activities of helicid derivatives. This compilation of 102 references may be helpful in understanding the diverse biological properties of helicid while providing insights into its mechanism of action. This may direct future research in the synthesis of new derivatives and the exploration of other biological activities.

(d)-Glucosamine and other nutritional supplements have emerged as safe alternative therapies for osteoarthritis, a chronic and degenerative articular joint disease. N-acetyl-(d)-glucosamine, a compound that can be modified at the N position, is considered to improve the oral bioavailability of (d)-glucosamine and has been proven to possess greater in vitro chondroprotective activity compared with the parent agent. In this study, to further utilize these properties, we focus on the modification of the N position with a benzenesulfonyl and different isoxazole formyl groups. Among these compounds, the 3-(2-chlorobenzene)-5-methyl-isoxazole formyl chloride and p-methoxybenzenesulfonyl chloride modifying structures proved to be the most active of the series and efficiently processed the chondrocytes in vitro. These novel N-position substitution compounds may represent promising leads for osteoarthritis drug development.

Recent studies showed that Guaiazulene (GA) and Sodium guaiazulene sulfonate (GAS-Na) have good anti-gastric ulcer effect. Here, two series of GA derivatives were synthesized and evaluated for their anti-gastric ulcer activity. The data obtained from in vivo testing of these compounds in a rodent ethanol-induced stomach injury model are discussed. Among the tested compounds, A1, A4, and A9 (ulcer index: 1.125 ± 1.246**, 1.714 ± 0.756*, 1.875 ± 1.126*) exhibited better anti-gastric ulcer activity than the positive control Omeprazole (2.005 ± 1.011*). The information got from these studies and the results of 3D-SAR investigation may be useful in the design of novel anti-gastric ulcer agents.

A new series of icariin derivatives were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. Most of the tested compounds exhibited high AChE inhibition and low toxicity, and among which compounds 1, 2, and 10 were the most potent (IC50 = 71.52 ± 22.43, 8.28 ± 1.45, 5.830 ± 1.78 nm, respectively).

A series of helicid derivatives with benzyl protection of the hydroxyl group at allopyranosyloxy was synthesized and evaluated for sedative-hypnotic activity. The structures of the new compounds were characterized by 1H NMR, IR, and HR-MS spectra. The sedative-hypnotic activities of the target compounds were evaluated using the spontaneous locomotor activity test in mice. Most of the derivatives have moderate to high activity; in particular, compound 3b presented the most potent sedative-hypnotic effect in comparison with the other derivatives, and derivatives 4c, 4d, and 4e also showed higher sedative-hypnotic activities.

This paper reports the synthesis of a new series of helicid–pyrrolidone derivatives (4a–4d, 5a–5d, and 6a–6d), which were tested for antitumor activity against human skov3 cell. In this study, two compounds (4b and 6c) demonstrate high antitumor activity against this cell line having IC50 values of 0.22 and 6.5 μM, respectively, which are lower than those of an inhibitor of heat shock protein 90 (17AAG), currently under clinical evaluation for cancer treatment.

Novel methyl 2-hydroxy-5-substituted benzoate derivatives (2a–2i) were synthesized by esterification of methyl gentisate and long-chain fatty acids. The compounds were structurally confirmed by MS, IR, 1H NMR, and HR-MS spectroscopy. A preliminary bioassay test demonstrated that compounds 2b, 2c, 2f, 2g, 2h showed stronger inhibition of tyrosinase activity. Further pharmacological experiments showed that after substitution modification of compounds 2b, 2f, 2g, and 2h, they have no potential toxicity and phototoxicity.

A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50 values of 25.5 and 35.2 μM against human hepatoma carcinoma cell lines, BEL-7402 and SMMC-7221, respectively. The anticancer activity of 4 was comparable to that of Tanespimycin (17-N-allylamino-17-demethoxy geldanamycin, 17-AAG) that inhibited the growth of BEL-7402 and SMMC-7221 cells at IC50 values of 12.4 and 9.85 μM, respectively. However, unlike allopurinol, which is also a strong inhibitor of XOD, compound 4 is a much weaker XOD inhibitor, suggesting that the anticancer activities of the allopurinol derivatives may not be associated with XOD inhibition. Moreover, the cytotoxicity of 4 toward normal cells is significantly lower than that of 17-AAG, making 4 a promising lead compound for further optimization of structure-activity relationships that may lead to anticancer agents of clinical utility.

New 4-chalcone ursolate and 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline-5-phenyl ursolate derivatives were synthesized by esterification of UA and chalcone or pyrazoline. The compounds were structurally confirmed by IR, 1H NMR, 13C NMR, and HR-MS spectroscopy. The cytotoxicity of ten derivatives was evaluated against A549, SKOV3, and HepG2 cell lines by MTT assay. The result showed that several compounds were more potent than UA against A549 and SKOV3 cells; however, none of them were more potent than UA against HepG2.

Seven helicid derivatives containing decahydroacridine-1,8-dione were prepared via the reactions between 1,3-cyclohexanedione or 5,5-dimethyl-1,3-cyclohexanedione and the corresponding Schiff base. The structures of the helicid derivatives were characterized by IR, 1H NMR, and HR-MS spectrum. The target compounds were evaluated by their hypnotic-sedative activity in vivo. The preliminary bioassay tests showed that some of the compounds had more potent activity than that of helicid.

Reactions of natural helicid with a number of 1,3-dicarbonyl compounds or β-ketoester in the presence of ammonium acetate or 1-naphthylamine gave a series of helicid derivatives containing a 1,4-dihydropyridine fragment (2a–2h). Eight novel helicid derivatives were structurally confirmed by IR, 1H NMR, 13C NMR, and HR-MS spectroscopy and evaluated for their sedative-hypnotic activities on mice. The results demonstrated that two compounds had higher sedative-hypnotic activity compared with helicid.

Under solvent-free conditions, syntheses of 2-aryl-4-(4-β-D-allopyranosyloxyphenyl)-4,6,7,8tetrahydroquinolin-5(1H)-one derivatives were carried out from chalcone (2a–2e), cyclohexane-1,3-dione (3), and NH4OAc in excellent yield without using any catalysts. The structure of the new compounds were characterized by 1H NMR, IR, and HR-MS spectroscopy. The preliminary bioassay tests of 4a–4j indicated that compounds 4b, 4e, and 4f exhibited potent sedative and hypnotic activity.

Using helicid as starting material, E-4-β-D-allopyranoside-cinnamic-4-substituted phenylketones (1a–1h) containing the structure of chalcones were synthesized; then these chalcones were reacted with guanidine hydrochloride through a 1,4-Michael reaction, giving 2-amino-4-(4-β-D-allopyranoside-phenyl)-6-3(4)substituted phenylpyrimidines (2a–2h), which were characterized by IR, 1H NMR, and HR-MS. The target compounds were evaluated by the spontaneous locomotor activity test, showing that all of them had good calming activity; compound 2f was found to have the greatest.

A series of novel helicid derivatives containing 3,4-dihydropyrimidin-2(1H)-one and 3,4-dihydropyrimidine2(1H)-thione moiety (3a–3f and 4a–4f) were synthesized starting from helicid. The structure of the new compounds were characterized by 1H NMR, IR and HR-MS spectra. The sedative-hypnotic activities of the target compounds were evaluated using the test of spontaneous locomotor activity in mice. All of the derivatives produced moderate to high activities; in particular, compound 4a presented the most potent sedative-hypnotic effect in comparison to the other derivatives, and derivatives 3a, 3c, 3d, 3e and 3f also showed potent activities.

5-(4'-β-D-Allopyranosyloxyphenyl)-3-aryl-4,5-dihydropyrazole-1-carbothioamides (2a–2h) were synthesized by the reaction of (1a–1h) with thiosemicarbazide and KOH in ethanol. The structures of all new compounds were characterized by 1HNMR, IR, and MS (HR-MS) spectra. A preliminary bioassay test of 1f–1h and 2a–2h suggested that most of these helicid analogues showed mild to strong activity. Compounds 1g, 2a, 2c, and 2f at a dose of 200 mg·kg–1 were better than that of the parent helicid.

E-(4-β-D-Allopyranosyloxyphenyl)-1-(4-substituted phenyl)propenone derivatives (1a–g) have been synthesized by the Claisen-Schmidt condensation of helicid with 4-substituted acetophenone using 10% NaOH aqueous solution as a catalyst. 6H-2-Amino-4-aryl-6-(4-β-D-allopyranosyloxyphenyl)-1,3-thiazine (2a–g) were synthesized by the 1,4-Michael reaction of 1a–g with thiourea. The structures of all the new products were established by 1H NMR, IR, and MS spectroscopy. Compound 2b (200 mg·kg–1) showed better sedative-hypnotic activity, so further modification of helicid should be worthwhile.

The mol-ecule of the title compound, C(14)H(19)N(3)O(7)·0.5H(2)O, exhibits an E conformation about the C=N double bond. The water mol-ecule possesses crystallographically imposed twofold symmetry. In the crystal structure, the mol-ecules are connected by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds into a three-dimensional network.

In the title compound, C18H18N2O3, the dihedral angle formed by the benzene rings is 71.75 (4)°. In the crystal structure, centrosymmetrically related molecules are linked into dimers by intermolecular O—H...O hydrogen bonds and π–π stacking interactions with centroid–centroid distances of 3.5511 (6) Å.

The title compound, C21H24O11, crystallizes exclusively as the β-anomer. The substituent of the protected sugar at position C-3 is in the axial position, while all other groups are in equatorial positions. The pyranoside ring adopts a stable chair conformation.

The title compound, C(21)H(21)BrO(7)·C(2)H(6)O, was synthesized by the Claisen-Schimidt reaction of helicid (systematic name: 4-formyl-phenyl-β-d-allopyran-oside) with 4-bromo-aceto-phenone in ethanol. The pyran ring adopts a chair conformation. In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular O-H⋯O hydrogen bonds.

The title compound, C(15)H(16)N(2), contains two aromatic rings linked through an imino group. The mol-ecule exhibits an E configuration with respect to the C=N bond. The dihedral angle between the aromatic rings is 61.96 (1)°.

The title compound, C(21)H(21)ClO(7)·C(2)H(5)OH was synthesized by the condensation reaction between helicid [systematic name: 4-(β-d-allopyranos-yloxy)benzaldehyde] and 4-chloro-aceto-phen-one in ethanol. In the mol-ecular structure, the pyran-oside ring adopts a chair conformation. In the crystal structure, the molecules are linked by inter-molecular O-H⋯O hydrogen bonds involving the OH groups from the pyran-oside unit and from the ethanol solvent mol-ecule.

The title compound, C(14)H(19)NO(6), was synthesized by the condensation reaction between hecilid (4-formyl-phenl-β-d-allopyran-oside) and methyl-amine in methanol. In the crystal structure, the pyran ring adopts a chair conformation and adjacent mol-ecules are linked by inter-molecular O-H⋯O and O-H⋯N hydrogen bonds, forming a three-dimensional network.

The title compound, C(34)H(54)O(5), was synthesized by the reaction of ursolic acid with ethyl chloro-acetate in the presence of DMA. All six-membered rings of the penta-cyclic triterpene skeleton adopt chair conformations. In the crystal structure, mol-ecules are linked by inter-molecular O-H⋯O hydrogen-bond inter-actions, forming zigzag chains along the c axis.