Mannich Bases: Centrality in Cytotoxic Drug Design

Bhilare, Neha V.; Marulkar, Vinayak S.; Shirote, Pramodkumar J.; Dombe, Shailaja; Pise, Vilas J.; Salve, Pallavi; Biradar, Shantakumar M.; Yadav, Vishal; Jadhav, Prakash D.; Bodhe, A.A.; Borkar, Smita P.; Ghadge, Prachi M.; Shelar, Pournima A.; Jadhav, Apurva V.; Godse, Kirti C.

doi:10.2174/1573406418666211220124119

Cited by 7 publications

(5 citation statements)

References 92 publications

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“…Mannich bases have been shown in several studies to have major biological effects such as anticancer, antibacterial, analgesic, antiviral, anti-inflammatory, anticonvulsant, anti-Alzheimer, anti-HIV, antimalarial, antioxidant, anthelmintic, etc. A variety of derivatives of ketonic Mannich bases were evaluated for their cytotoxicity against Jurkat cells and androgen-independent prostate cancer cells (PC-3) [23]. Analogs of Mannich bases of heterocyclic chalcone have been studied for their cytotoxic activity against four human cancer cell lines, namely, PC-3, MCF-7, nasopharyngeal carcinoma (KB), and resistant nasopharyngeal carcinoma (KB-VIN) [24].…”

Section: Introductionmentioning

confidence: 99%

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases

Mutahir

Khan

Mushtaq³

et al. 2023

Molecules

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Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases

Mutahir

Khan

Mushtaq³

et al. 2023

Molecules

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“…Further researchers who also studied this type of condensation before Mannich, are van Marle and Tollens [11], Schäfer and Tollens [12], Auwers and Dombrowski [13], and Petrenko-Kritschenko and 2 of 35 his co-workers [14][15][16][17]. In recent times, the procedure has garnered notable consideration due to the versatile nature of its constituents, the use of gentle reaction conditions, and the potential pharmacological activity of the final products [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Bioactive Aminomethylated 8-Hydroxyquinolines via the Modified Mannich Reaction

Csuvik

Szatmári

2023

IJMS

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8-hydroxyquinoline (oxine) is a widely known and frequently used chelating agent, and the pharmacological effects of the core molecule and its derivatives have been studied since the 19th century. There are several synthetic methods to modify this core. The Mannich reaction is one of the most easily implementable examples, which requires mild reaction conditions and simple chemical reagents. The three components of the Mannich reaction are a primary or secondary amine, an aldehyde and a compound having a hydrogen with pronounced activity. In the modified Mannich reaction, naphthol or a nitrogen-containing naphthol analogue (e.g., 8-hydroxyquinoline) is utilised as the active hydrogen provider compound, thus affording the formation of aminoalkylated products. The amine component can be ammonia and primary or secondary amines. The aldehyde component is highly variable, including aliphatic and aromatic aldehydes. Based on the pharmacological relevance of aminomethylated 8-hydroxyquinolines, this review summarises their syntheses via the modified Mannich reaction starting from 8-hydroxyquinoline, formaldehyde and various amines.

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“…Additionally, these phytochemicals modulate cell proliferation and apoptosis signaling pathways in transformed cells, contributing to their potential as valuable candidates for cancer treatment and prevention. 6,7 A. squamosa L. called as custard apple is an evergreen tree with a height ranging from 3-8 meters. Its leaves are oblonglanceolate or lanceolate, measuring 6-17 cm in length and 3 to 5 cm in width, arranged alternately on short petioles.…”

Section: Introductionmentioning

confidence: 99%

Isolation, In-silico Studies, and Biological Evaluation of Higenamine from Annona squamosa L. against Breast Cancer

Shailaja,

Pramodkumar

2023

IJPQA

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The efficacy of Annona squamosa L. in cancer treatment has been documented, inspiring the authors to investigate the plant further for potential novel anticancer compounds. Therefore, the current study aimed to isolate and characterize Higenamine from leaves extract of A. squamosa L. and studied for the in-vitro cancer cell line and molecular docking. The high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) method development of A. squamosa L. leaves extract furnished Higenamine of which characterization was established by HPLC, infrared radiation (IR), liquid chromatography-mass spectrometry (LC-MS) and its acute toxicity study and cytotoxic properties using MCF-7 cell lines by MTT assay were assessed. Molecular docking was done using Auto Dock Vina software to validate the anticancer activity. The extraction batches by ultrasonication and maceration methods showed good results using 80% methanol. Acute toxicity studies, after a single dose (2000 mg/kg) administration of methanolic extract don’t show clinical symptoms of toxicity and mortalities. From the extract, Higenamine was eluted and the dried fraction showed 66% of enrichment of Higenamine. The developed HPLC and TLC methods showed Higenamine (HGN) peak at 6.21 minutes band at Rf 0.61, respectively. The isolated compound was identified as Higenamine with FTIR spectroscopic analysis which revealed various characteristic band values with functional groups. HPLC-MS showed m/z at 272.1 (M+H+) corresponding to the molecular formula C16H17NO3. The IC50 value for Higenamine was 42.39 μg/mL were observed in MCF-7 breast cancer which was better than 5-Fluorouracil having 39.22 μg/mL. In-silico studies explored that higenamine showed good binding affinity to breast cancer PDBIDs and forms a stable complex. Furthermore, absorption, distribution, metabolism, and excretion (ADME) properties of isolated compound was calculated using the Swiss ADME online tool in which higenamine was found to have a good pharmacokinetic profile as compared with 5-fluorouracil and doxorubicin. Higenamine has been isolated and identified as a potential anticancer agent. Further research can explore its effectiveness through pharmaceutical formulation and in vitro cell line studies.

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Mannich Bases: Centrality in Cytotoxic Drug Design

Cited by 7 publications

References 92 publications

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases

Synthesis of Bioactive Aminomethylated 8-Hydroxyquinolines via the Modified Mannich Reaction

Isolation, In-silico Studies, and Biological Evaluation of Higenamine from Annona squamosa L. against Breast Cancer

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