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Two new steroidal alkaloids, salonine-A [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-14-en-2beta,4beta-diol] (1), and salonine-B [(20S)-20-(N,N-dimethylamino)-3beta-methoxy-pregn-5,16-diene] (2), were isolated from the MeOH extract of Sarcococca saligna, along with a known base, alkaloid-C (3). Their structures were elucidated on...
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... In contrast to AChE, BChE lacks Trp279 resulting in weaker binding of bisquaternary ligands at the PAS. The ChE is known to be inhibited by a wide variety of synthetic and natural compounds (Houghton et al., 2006;Murray et al., 2013), and previously, several natural ChE inhibitors isolated from various medicinal plants were reported by our group (Parveen et al., 2001;Atta-ur-Rahman et al., 2002;Atta-Ur-Rahman et al., 2003;Choudhary et al., 2006). The in vitro and in silico studies aimed to perform inhibition kinetics, Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Indices (CoMSIA), ligand docking, and molecular dynamics (MD) simulation studies have also been conducted on these inhibitors Wheeler, 2003;Zaheer et al., 2003). ...
Currently, acetylcholinesterase (AChE) inhibiting drugs in clinical use, such as tacrine, donepezil, rivastigmine, and galanthamine, are associated with serious side effects and short half-lives. In recent years, numerous phytochemicals have been identified as inhibitors of cholinesterases with potential applications in the management of Alzheimer’s disease (AD). In this study three natural coumarins, 2′-O-ethylmurrangatin ( 1 ), murranganone ( 2 ), and paniculatin ( 3 ) isolated previously by our group from the leaves of Murraya paniculata, were tested against the two cholinesterases (ChE) enzymes, AChE and butyrylcholinesterase (BChE) using in vitro assay. Molecular docking was performed to highlight the structural properties that contribute to the molecular recognition pattern in the inhibition of ChE and the structural differences resulting in the selectivity of these compounds toward AChE. Classical enzyme inhibition kinetics data suggested that compounds 2 and 3 were potent inhibitors of AChE and BChE, while 1 was found inactive against both enzymes. The findings from molecular docking studies revealed the competitive and non-competitive inhibition mechanisms of compounds 2 and 3 against both enzymes. Molecular docking and simulations have revealed that hydrogen bonding, mediated by ketone and hydroxyl functionalities in various positions, significantly contributes to the binding of the inhibitor to the receptor. According to MD simulation studies, the stability of the ligand-AChE complex for the most active compound ( 3 ) is found to be comparable to that of the widely used drug Tacrine. In addition, to evaluate the drug-likeness of compounds, in silico ADME evaluation was performed, and the compounds presented good ADME profiles. Data suggested that the coumarin nucleus having diverse side chains at the C-8 position can serve as a potential inhibitor of cholinesterases and can act as a lead to develop a new semisynthetic drug for the treatment of AD.
... N-methylfuntumafrine (172) shows a novel structure with an acetyl group at C-17 [47]. 46 Sarconidine R 1 = H; R 2 = β-NHCH 3 ; R 3 = CH 3 S. saligna [49] 47 Salonine B R 1 = H; R 2 = β-OCH 3 ; R 3 = CH 3 S. saligna [50] 48 Salignamine ...
... Pachysandra axillaris [53] 55 Paxillarine B R 1 = Bz; R 2 = R 7 = CH 3 ; R 3 = β-OAc; R 4 = R 6 = H; R 5 = β-OH P. axillaris [53] 56 Pachysamine B R 1 = Sen; R 2 = R 7 = CH 3 ; R 3 = R 4 = R 5 = R 6 = H P. procumbens [46] 57 Pachysamine E R 1 = Sen; R 2 = R 3 = R 4 = R 5 = R 6 = H; R 7 = CH 3 P. terminalis [54] 58 (+)-(20S)-20-(Dimethylamino)-3α-(methylbenzoylamino)-11-methylene-5αpregnane [57] 63 Pachyaximine A R 1 = R 3 = R 4 = H; R 2 = OCH 3 ; R 5 = R 6 = CH 3 S. saligna; P. procumbens [46,48] S. saligna [58] 66 Epipachysamine-E-5-en-4-one R 1 = R 4 = H; R 2 = NH-Sen; R 3 = O; R 5 = R 6 = CH 3 S.brevifolia [59] 67 N b -Demethylepipachysamine-E-5-ene-4-one R 1 = R 4 = R 5 = H; R 2 = NH-Sen; R 3 = O; R 6 = CH 3 S. brevifolia [59] 68 Salignarine B R 1 = β-OH; R 2 = NH-Tig; R 3 = R 4 = H; R 5 = R 6 = CH 3 S. saligna [44] 69 Salignarine C R 1 = β-OH; R 2 = NH-Sen; R 3 = R 4 = H; R 5 = R 6 = CH 3 S. saligna [44] 70 Iso-N-formylchonemorphin-5-ene R 1 = R 3 = R 4 = R 5 = H; R 2 = N(CH 3 ) 2 ; R 6 = CHO S. zeylanica [60] 71 Alkaloid C R 1 = R 3 = R 4 = H; R 2 = OCH 3 ; R 5 = R 6 = CH 3 S. saligna [50] 72 Salignarine F R 1 = R 4 = H; R 2 = NH-Tig; R 3 = β-OH; R 5 = R 6 = CH 3 S. saligna [51] 73 Saracosine R 1 = R 3 = R 4 = H; R 2 = N(CH 3 ) 2 ; R 5 = Ac; R 6 = CHO S. saligna [51] 74 Sarcodinine ...
... S. saligna [50] 99 Dictyophlebine [51,65] 100 [71] 104 Hookerianamide D R 1 = R 4 = H; R 2 = R 5 = CH 3 ; R 3 = COCHC(CH 3 ) CH(CH 3 )CH 3 ; R 6 = CHO S. hookeriana [73] 105 Hookerianamide E R 1 = β-OAc; R 3 = R 4 = H; R 2 = Sen; R 5 = R 6 = CH 3 ; △ 14,15 S. hookeriana [73] 106 Hookerianamide G R 1 = H; R 2 = R 5 = R 6 = CH 3 ; R 3 = Bz; R 4 = β-OAc S. hookeriana [73] 107 Hookerianamide I R 1 = R 4 = R 5 = H; R 2 = R 6 = CH 3 ; R 3 = Bz S. hookeriana [74] 108 Chonemorphine R 1 = R 2 = R 3 = R 4 = H; R 5 = R 6 = CH 3 S. hookeriana [65] 109 N-Methypachysamine A R 1 = R 4 = H; R 2 = R 3 = R 5 = R 6 = CH 3 S. hookeriana [65] 110 Pachysamine J R 1 = α-OH; R 2 = R 4 = H; R 3 = Sen; R 5 = R 6 = CH 3 Pachysandra axillaris [75] 111 Pachysamine O R 1 = R 2 = R 4 = H; R 3 = Cin; R 5 = R 6 = CH 3 P. axillaris [75] 112 Pachysamine P R 1 = R 2 = H; R 3 = COCH 2 C(CH 3 )C(CH 3 )CH 3 ; R 4 = β-OH; R 5 = R 6 = CH 3 P. axillaris [75] 113 (20S)-2α,4β-Bis(acetoxy)-20-(N,N-dimethylamino)-3β-tigloylamino-5α-pregnane R 1 = α-OAc; R 2 = H; R 3 = Tig; R 4 = β-OAc; [77] 116 [75] 126 Pachysamine M R 1 = Sen; R 2 = O; R 3 = R 4 = H; R 5 = CH 3 P. axillaris [75] 127 Pachysamine N R 1 = Sen; R 2 = O; R 3 = H; R 4 = β-OH; R 5 = CH 3 P. axillaris [75] 128 Sarsaligenine A R 1 = Sen; R 2 = O; R 3 = R 4 = H; R 5 = CH 3 ; △ 16,17 Sarcococca saligna [79] 129 Sarsaligenine B R 1 = Sen; R 2 = O; R 3 = α-OH; R 4 = H; R 5 = CH 3 S. saligna [79] 130 Sarcovagenines A R 1 = R 3 = β-OH; R 2 = Tig; R 4 = CH 3 S. vegans [78] 131 Sarcovagenines B R 1 = α-OH; R 2 = Tig; R 3 = β-OAc; R 4 = CH 3 S. vegans [78] 132 Salignarine D R 1 = R 3 = H; R 2 = Sen; R 4 = CH 3 S. saligna [44] 133 (−)-Vaganine D R 1 = H; R 2 = Sen; R 3 = β-OAc; R 4 = CH 3 S. coriacea [80] 134 (+)-Nepapakistamine A R 1 = R 3 = β-OAc; R 2 = Tig; R 4 = H S. coriacea [80] 135 5,6-Dihydrosarconidine 143 E-salignone S. saligna [65] 144 Z-salignone S. saligna [65] 145 Holamine ...
Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule. They have demonstrated a wide range of biological activities, and some of them have even been developed as therapeutic drugs, such as abiraterone acetate (Zytiga®), a blockbuster drug, which has been used for the treatment of prostate cancer. Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities, which are attractive for natural product chemistry and medicinal chemistry communities. This review comprehensively covers the structural classification, isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021, with 363 references being cited.
... N-methylfuntumafrine (172) shows a novel structure with an acetyl group at C-17 [47]. 46 Sarconidine R 1 = H; R 2 = β-NHCH 3 ; R 3 = CH 3 S. saligna [49] 47 Salonine B R 1 = H; R 2 = β-OCH 3 ; R 3 = CH 3 S. saligna [50] 48 Salignamine ...
... Pachysandra axillaris [53] 55 Paxillarine B R 1 = Bz; R 2 = R 7 = CH 3 ; R 3 = β-OAc; R 4 = R 6 = H; R 5 = β-OH P. axillaris [53] 56 Pachysamine B R 1 = Sen; R 2 = R 7 = CH 3 ; R 3 = R 4 = R 5 = R 6 = H P. procumbens [46] 57 Pachysamine E R 1 = Sen; R 2 = R 3 = R 4 = R 5 = R 6 = H; R 7 = CH 3 P. terminalis [54] 58 (+)-(20S)-20-(Dimethylamino)-3α-(methylbenzoylamino)-11-methylene-5αpregnane [57] 63 Pachyaximine A R 1 = R 3 = R 4 = H; R 2 = OCH 3 ; R 5 = R 6 = CH 3 S. saligna; P. procumbens [46,48] S. saligna [58] 66 Epipachysamine-E-5-en-4-one R 1 = R 4 = H; R 2 = NH-Sen; R 3 = O; R 5 = R 6 = CH 3 S.brevifolia [59] 67 N b -Demethylepipachysamine-E-5-ene-4-one R 1 = R 4 = R 5 = H; R 2 = NH-Sen; R 3 = O; R 6 = CH 3 S. brevifolia [59] 68 Salignarine B R 1 = β-OH; R 2 = NH-Tig; R 3 = R 4 = H; R 5 = R 6 = CH 3 S. saligna [44] 69 Salignarine C R 1 = β-OH; R 2 = NH-Sen; R 3 = R 4 = H; R 5 = R 6 = CH 3 S. saligna [44] 70 Iso-N-formylchonemorphin-5-ene R 1 = R 3 = R 4 = R 5 = H; R 2 = N(CH 3 ) 2 ; R 6 = CHO S. zeylanica [60] 71 Alkaloid C R 1 = R 3 = R 4 = H; R 2 = OCH 3 ; R 5 = R 6 = CH 3 S. saligna [50] 72 Salignarine F R 1 = R 4 = H; R 2 = NH-Tig; R 3 = β-OH; R 5 = R 6 = CH 3 S. saligna [51] 73 Saracosine R 1 = R 3 = R 4 = H; R 2 = N(CH 3 ) 2 ; R 5 = Ac; R 6 = CHO S. saligna [51] 74 Sarcodinine ...
... S. saligna [50] 99 Dictyophlebine [51,65] 100 [71] 104 Hookerianamide D R 1 = R 4 = H; R 2 = R 5 = CH 3 ; R 3 = COCHC(CH 3 ) CH(CH 3 )CH 3 ; R 6 = CHO S. hookeriana [73] 105 Hookerianamide E R 1 = β-OAc; R 3 = R 4 = H; R 2 = Sen; R 5 = R 6 = CH 3 ; △ 14,15 S. hookeriana [73] 106 Hookerianamide G R 1 = H; R 2 = R 5 = R 6 = CH 3 ; R 3 = Bz; R 4 = β-OAc S. hookeriana [73] 107 Hookerianamide I R 1 = R 4 = R 5 = H; R 2 = R 6 = CH 3 ; R 3 = Bz S. hookeriana [74] 108 Chonemorphine R 1 = R 2 = R 3 = R 4 = H; R 5 = R 6 = CH 3 S. hookeriana [65] 109 N-Methypachysamine A R 1 = R 4 = H; R 2 = R 3 = R 5 = R 6 = CH 3 S. hookeriana [65] 110 Pachysamine J R 1 = α-OH; R 2 = R 4 = H; R 3 = Sen; R 5 = R 6 = CH 3 Pachysandra axillaris [75] 111 Pachysamine O R 1 = R 2 = R 4 = H; R 3 = Cin; R 5 = R 6 = CH 3 P. axillaris [75] 112 Pachysamine P R 1 = R 2 = H; R 3 = COCH 2 C(CH 3 )C(CH 3 )CH 3 ; R 4 = β-OH; R 5 = R 6 = CH 3 P. axillaris [75] 113 (20S)-2α,4β-Bis(acetoxy)-20-(N,N-dimethylamino)-3β-tigloylamino-5α-pregnane R 1 = α-OAc; R 2 = H; R 3 = Tig; R 4 = β-OAc; [77] 116 [75] 126 Pachysamine M R 1 = Sen; R 2 = O; R 3 = R 4 = H; R 5 = CH 3 P. axillaris [75] 127 Pachysamine N R 1 = Sen; R 2 = O; R 3 = H; R 4 = β-OH; R 5 = CH 3 P. axillaris [75] 128 Sarsaligenine A R 1 = Sen; R 2 = O; R 3 = R 4 = H; R 5 = CH 3 ; △ 16,17 Sarcococca saligna [79] 129 Sarsaligenine B R 1 = Sen; R 2 = O; R 3 = α-OH; R 4 = H; R 5 = CH 3 S. saligna [79] 130 Sarcovagenines A R 1 = R 3 = β-OH; R 2 = Tig; R 4 = CH 3 S. vegans [78] 131 Sarcovagenines B R 1 = α-OH; R 2 = Tig; R 3 = β-OAc; R 4 = CH 3 S. vegans [78] 132 Salignarine D R 1 = R 3 = H; R 2 = Sen; R 4 = CH 3 S. saligna [44] 133 (−)-Vaganine D R 1 = H; R 2 = Sen; R 3 = β-OAc; R 4 = CH 3 S. coriacea [80] 134 (+)-Nepapakistamine A R 1 = R 3 = β-OAc; R 2 = Tig; R 4 = H S. coriacea [80] 135 5,6-Dihydrosarconidine 143 E-salignone S. saligna [65] 144 Z-salignone S. saligna [65] 145 Holamine ...
Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule. They have demonstrated a wide range of biological activities, and some of them have even been developed as therapeutic drugs, such as abiraterone acetate (Zytiga®), a blockbuster drug, which has been used for the treatment of prostate cancer. Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities, which are attractive for natural product chemistry and medicinal chemistry communities. This review comprehensively covers the structural classification, isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021, with 363 references being cited.
... The structures of compounds 3 [8], 4 [5,9], 5 [10], 6 [11], and 7 [12] were confirmed by comparing their spectral data with reported data in the literature. ...
Bio-assay guided isolation from the plant Sarcococca wallichii Staph. yielded two new steroidal alkaloids: wallichimine A (1) and wallichimine B (2), and five known ones: sarcodinine (3), N-methylpachysamine A (4), alkaloid C (5), dictyophlebine (6), and sarcorine (7). The structures of the compounds were determined using mass spectrometry and NMR spectroscopy techniques. The immunomodulatory potential of compounds was evaluated on different parameters including production of intracellular reactive oxygen species (ROS), nitric oxide (NO) and on proinflammatory cytokine TNF-α. All compounds were found to be potent inhibitors of intracellular ROS produced from isolated neutrophils, except compound 5, which showed a moderate level of inhibition. Compounds 2 and 4 potently inhibited the production of NO (67.9% and 62.5% respectively). Compound 2 showed potent suppression on production of proinflammatory cytokine TNF-α (76.7%). Among all the tested compounds the new compound 2 was found to be the most potent immunosuppressive agent. This study shows that steroidal alkaloids could be lead compounds for anti-inflammatory drug discovery.
... The structures of compounds 3 [8], 4 [5,9], 5 [10], 6 [11], and 7 [12] were confirmed by comparing their spectral data with reported data in the literature. ...
Bio-assay guided isolation from the plant Sarcococca wallichii Staph. yielded two new steroidal alkaloids: wallichimine A (1) and wallichimine B (2), and five
known ones: sarcodinine (3), N-methylpachysamine A (4), alkaloid C (5), dictyophlebine (6), and sarcorine (7). The structures of the compounds were
determined using mass spectrometry and NMR spectroscopy techniques. The immunomodulatory potential of compounds was evaluated on different
parameters including production of intracellular reactive oxygen species (ROS), nitric oxide (NO) and on proinflammatory cytokine TNF-α. All compounds
were found to be potent inhibitors of intracellular ROS produced from isolated neutrophils, except compound 5, which showed a moderate level of inhibition.
Compounds 2 and 4 potently inhibited the production of NO (67.9% and 62.5% respectively). Compound 2 showed potent suppression on production of
proinflammatory cytokine TNF-α (76.7%). Among all the tested compounds the new compound 2 was found to be the most potent immunosuppressive agent.
This study shows that steroidal alkaloids could be lead compounds for anti-inflammatory drug discovery.
... New steroidal alkaloid AChEi from S. saligna and S. hookeriana were recently found. In the case of S. saligna, the study -which was a continuation of previous research [44,45]-of the bioactive steroidal alkaloids of this species allowed the isolation of five new compounds (89)(90)(91)(92)(93) and two already known bases (94 and 95) [46]. The new alkaloids 5,14-dehydro-N a -demethylsaracodine (89), 14dehydro-N a -demethylsaracodine (90) [43,49]. ...
As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer’s disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery of an important number of secondary metabolites and plant extracts with the ability of inhibiting the enzyme AChE, which, according to the cholinergic hypothesis, increases the levels of the neurotransmitter acetylcholine in the brain, thus improving cholinergic functions in patients with Alzheimer’s disease and alleviating the symptoms of this neurological disorder. This review summarizes a total of 128 studies which correspond to the most relevant research work published during 2006-2012
(1st semester) on plant-derived compounds, plant extracts and essential oils found to elicit AChE inhibition.
... Therefore, compound 3 was identified as (20S)-2α, 4β-bis (acetoxy)-20-(N,N-dimethylamino)-3β-tigloylamino-5αpregnane (Fig. 1). The known compounds isolated were characterized to be 11-hydroxyepipachysamine-E (4) [12], (2α, 3β, 4β, 20S)-2, 4-bis(acetoxy)-20-(N, N-dimethylamino)-3-[(3-methylbut-2-enoyl) amino]-5α-pregnane (5) [13], vagnine B (6) [14], (20S)-20-(N, N-dimethylamino)-3β-methoxy-pregn-5-ene (7) [15], (+)-irehine (8) [16], axillaridine A (9) [17], epi-pachysamine B (10) [14], salonine B (11) [18], funtumafrine C (12) [19], pachysamine M (13) [20], and hookerianamide B (14) [13] (Fig. 1). ...
... The cholinesterase inhibitory activities, represented by IC 50 (μM), were obtained from recently published data (Atta ur, Choudhary, 2000, Atta ur et al., 2003, Atta ur et al., 1997, Atta ur, Zaheer ul, 2002, Kalauni, Choudhary, 2001) (Table 1). The structures of inhibitors are presented inTable 2. The pIC 50 (logIC 50 ) values were used to derive 3D-QSAR models. ...
... The cholinesterase inhibitory activities, represented by IC 50 (μM), were obtained from recently published data (Atta ur, Choudhary, 2000, Atta ur et al., 2003, Atta ur et al., 1997, Atta ur, Zaheer ul, 2002, Kalauni, Choudhary, 2001 (Table 1). The structures of inhibitors are presented in Table 2. ...
... The acute toxicity (LD 50 ) of this alkaloid in mouse (s.c.) was found to be 40 mg/kg, which is less than the standard pysostigmine or neostigmine [2]. Previous phytochemical investigations on genus Sarcococca have resulted in the isolation of a number of steroidal alkaloids with a variety of biological activities3456789101112131415. We have reported various compounds from S. saligna, with potent acetylcholinesterase inhibitory activity [14,15] . ...
... Previous phytochemical investigations on genus Sarcococca have resulted in the isolation of a number of steroidal alkaloids with a variety of biological activities3456789101112131415. We have reported various compounds from S. saligna, with potent acetylcholinesterase inhibitory activity [14,15] . In continuation of our efforts aimed to isolate bioactive steroidal alkaloids, we have recently isolated five new steroidal alkaloids 1–5 from this plant along with two known bases 6 and 7 (Fig. 1 ). ...
Five new steroidal alkaloids, 5,14-dehydro-N(a)-demethylsaracodine [3beta-N(a)-methyl-20S-N(b)-acetyl-N(b)-methylamino-pregn-5,14-diene] (1), 14-dehydro-N(a)-demethylsaracodine [3beta-N(a)-methyl-20S-N(b)-acetyl-N(b)-methylamino-5alpha-pregn-14-ene] (2), 16-dehydrosarcorine [(20S)-20-(N,N-dimethylamino)-3beta-(N(a)-acetylamido)-5alpha-pregn-16-ene] (3), 2,3-dehydrosarsalignone [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-pregn-2,5-diene-4-one] (4), and 14,15-dehydrosarcovagine-D [(20S)-20-(N,N-dimethylamino)-3beta-(tigloylamino)-5alpha-pregn-2,14-diene-4-one] (5), were isolated from the ethanolic extract of Sarcococca saligna, along with two known bases, sarcovagenine-C (6) and salignarine-C (7). Their structures were elucidated on the basis of spectroscopic methods. All seven compounds were found to possess cholinesterase inhibitory potential in a concentration-dependent manner with the IC50 values ranging from 12.5 to 200 microM against acetylcholinesterase and from 1.25 to 32.2 microM against butyrylcholinesterase.
