Table Info

Table 2.

Physicochemical and drug-likeness properties of identified phytochemicals of C. cauliflora

Property	Results (SwissADME and Molinspiration)
Property	Procyanidin tetramer	Vitexin	β-Sitosterol acetate	Catechin	K-3-Rh
Molecular formula	C₆₀H₅₀O₂₄	C₂₁H₂₀O₁₀	C₃₁H₅₂O₂	C₁₅H₁₄O₆	C₂₁H₂₀O₁₀
Molecular weight	1,155.02 g/mol	432.38 g/mol	456.74 g/mol	290.27 g/mol	432.38 g/mol
Hydrogen bond (H-bond) donors	20	7	0	5	6
H-bond acceptors	24	10	2	6	10
Rotatable bonds	7	3	8	1	3
Log P (partition coefficient, predicted value)	2.11 or 5.0	–0.02 or 0.52	7.63 or 8.94	0.85 or 1.37	0.60 or 1.13
Lipinski’s rule of five	No	Yes	Yes	Yes	Yes
Ghose filter	No	Yes	No	Yes	Yes
Veber’s rule	No	No	Yes	Yes	No
Egan	No	No	No	Yes	No
Muegge filter	No	No	No	Yes	No
BBB permanent	No	No	No	No	No
CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 inhibitors	No	No	No	No	No
Bioavailability score	0.17	0.55	0.55	0.55	0.55

BBB: blood brain barrier; CYP1A2: cytochrome P450 1A2

Declarations

Author contributions

JI, HKSdZ, NY, and TCB: Conceptualization, Investigation, Writing—original draft. VYW: Validation, Writing—review & editing, Supervision. All authors read and approved the final version of the manuscript.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Data from the present manuscript will be made available upon reasonable request.

Funding

This research was funded by the Research for Oracle Program of University of Rajarata, Sri Lanka. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Ado MA, Abas F, Ismail IS, Ghazali HM, Shaari K. Chemical profile and antiacetylcholinesterase, antityrosinase, antioxidant and α-glucosidase inhibitory activity of Cynometra cauliflora L. leaves. J Sci Food Agric. 2015;95:635–42. [DOI] [PubMed]

Ado MA, Mediani A, Maulidiani, Ismail IS, Ghazali HM, Abas F. Flavonoids from Cynometra cauliflora and their antioxidant, α-glucosidase, and cholinesterase inhibitory activities. Chem Nat Compd. 2019;55:112–4. [DOI]

Khoo HE, Azlan A, Kong KW, Ismail A. Phytochemicals and medicinal properties of indigenous tropical fruits with potential for commercial development. Evid Based Complement Alternat Med. 2016;2016:7591951. [DOI] [PubMed] [PMC]

Abd Aziz AF, Bhuiyan MSA, Iqbal M. An evaluation of antioxidant and antidiabetic potential of Cynometra cauliflora (nam-nam, fabaceae). Trans Sci Technol. 2017;4:372–83.

Rabeta MS, Nur Faraniza R. Total phenolic content and ferric reducing antioxidant power of the leaves and fruits of Garcinia atrovirdis and Cynometra cauliflora. Int Food Res J. 2013;20:1691–6.

Samling BA, Assim Z, Tong WY, Leong CR, Ab Rashid S, Nik Mohamed Kamal NNS, et al. Cynometra cauliflora L.: an indigenous tropical fruit tree in Malaysia bearing essential oils and their biological activities. Arabian J Chem. 2021;14:103302. [DOI]

Dahanayake N. Some neglected and underutilized fruit-crops in Sri Lanka. IJSRP. 2015;5:165–71.

Kostermans AJGH. The genus Cynometra (Leguminosae) in Ceylon. REIN WARDTIA. 1982;10:63–8.

Lim TK. Cynometra cauliflora. In: Lim TK, editor. Edible medicinal and non-medicinal plants: volume 2, fruits. Dordrecht: Springer Netherlands; 2012. pp. 614–6. [DOI]

10.

Marbawi H, Ahmad SNS, Baharudin NS, Gansau JA. In vitro embryo germination and callus induction of Cynometra cauliflora, an underutilized medicinal plant. Trans Sci Technol. 2016;3:476–82.

11.

Seyedan A, Mohamed Z, Alshagga MA, Koosha S, Alshawsh MA. Cynometra cauliflora Linn. Attenuates metabolic abnormalities in high-fat diet-induced obese mice. J Ethnopharmacol. 2019;236:173–82. [DOI] [PubMed]

12.

Sukandar D, Nurbayti S, Rudiana T, Husna TW. Isolation and structure determination of antioxidants active compounds from ethyl acetate extract of heartwood namnam (Cynometra cauliflora L.). J Kim Terap Indones. 2017;19:11–7.

13.

Ong CW, Chan YS, Khoo KS, Ong HC, Sit NW. Antifungal and cytotoxic activities of extracts obtained from underutilised edible tropical fruits. Asian Pac J Trop Biomed. 2018;8:313–9. [DOI]

14.

Wahab NZA, Azizul A, Badya N, Ibrahim N. Antiviral activity of an extract from leaves of the tropical plant Cynometra cauliflora. Pharmacogn J. 2021;13:752–7. [DOI]

15.

Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. Alzheimer’s disease. Lancet. 2011;377:1019–31. [DOI] [PubMed]

16.

Awasthi M, Singh S, Tiwari S, Pandey VP, Dwivedi UN. Computational approaches for therapeutic application of natural products in Alzheimer’s disease. In: Roy K, editor. Computational modeling of drugs against Alzheimer’s disease. New York: Springer; 2018. pp. 483–511. [DOI]

17.

Mozaffarnia S, Teimuri-Mofrad R, Rashidi MR. Design, synthesis and biological evaluation of 2,3-dihydro-5,6-dimethoxy-1H-inden-1-one and piperazinium salt hybrid derivatives as hAChE and hBuChE enzyme inhibitors. Eur J Med Chem. 2020;191:112140. [DOI] [PubMed]

18.

Nirogi R, Shinde A, Kambhampati RS, Mohammed AR, Saraf SK, Badange RK, et al. Discovery and development of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (SUVN-502): a novel, potent, selective and orally active serotonin 6 (5-HT₆) receptor antagonist for potential treatment of Alzheimer’s Disease. J Med Chem. 2017;60:1843–59.

19.

Zhang X, He X, Chen Q, Lu J, Rapposelli S, Pi R. A review on the hybrids of hydroxycinnamic acid as multi-target-directed ligands against Alzheimer’s disease. Bioorg Med Chem. 2018;26:543–50. [DOI] [PubMed]

20.

Manavalan P, Taylor P, Johnson WC Jr. Circular dichroism studies of acetylcholinesterase conformation. Comparison of the 11 S and 5.6 S species and the differences induced by inhibitory ligands. Biochim Biophys Acta. 1985;829:365–70. [DOI] [PubMed]

21.

Zimmerman G, Soreq H. Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission. Cell Tissue Res. 2006;326:655–69. [DOI] [PubMed]

22.

Awasthi M, Singh S, Pandey VP, Dwivedi UN. Alzheimer’s disease: an overview of amyloid beta dependent pathogenesis and its therapeutic implications along with in silico approaches emphasizing the role of natural products. J Neurol Sci. 2016;361:256–71. [DOI] [PubMed]

23.

Mortier J, Rakers C, Bermudez M, Murgueitio MS, Riniker S, Wolber G. The impact of molecular dynamics on drug design: applications for the characterization of ligand–macromolecule complexes. Drug Discov Today. 2015;20:686–702. [DOI] [PubMed]

24.

Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today: Technol. 2004;1:337–41. [DOI] [PubMed]

25.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46:3–26. [DOI] [PubMed]

26.

Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09, revision C. 01. Wallingford: Gaussian Inc; 2009.

27.

Zhou Y, Fu Y, Yin W, Li J, Wang W, Bai F, et al. Kinetics-driven drug design strategy for next-generation acetylcholinesterase inhibitors to clinical candidate. J Med Chem. 2021;64:1844–55. [DOI] [PubMed]

28.

Allen WJ, Balius TE, Mukherjee S, Brozell SR, Moustakas DT, Lang PT, et al. DOCK 6: impact of new features and current docking performance. J Comput Chem. 2015;36:1132–56. [DOI] [PubMed] [PMC]

29.

Hess B, Kutzner C, van der Spoel D, Lindahl E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput. 2008;4:435–47. [DOI] [PubMed]

30.

Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013;29:845–54. [DOI] [PubMed] [PMC]

31.

Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. GROMACS: fast, flexible, and free. J Comput Chem. 2005;26:1701–18. [DOI] [PubMed]

32.

Schmid N, Eichenberger AP, Choutko A, Riniker S, Winger M, Mark AE, et al. Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur Biophys J. 2011;40:843–56. [DOI] [PubMed]

33.

Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J. Interaction models for water in relation to protein hydration. In: Pullman B, editor. Intermolecular Forces. Dordrecht: Springer Netherlands; 1981. pp. 331–42. [DOI]

34.

Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A smooth particle mesh Ewald method. J Chem Phys. 1995;103:8577–93. [DOI]

35.

Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to an external bath. J Chem Phys. 1984;81:3684–90. [DOI]

36.

Hess B, Bekker H, Berendsen HJC, Fraaije JGEM. LINCS: a linear constraint solver for molecular simulations. J Comput Chem. 1998;18:1463–72. [DOI]

37.

Sayle RA, Milner-White EJ. RASMOL: biomolecular graphics for all. Trends Biochem Sci. 1995;20:374–6. [DOI] [PubMed]

38.

Laskowski RA, Swindells MB. LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J Chem Inf Model. 2011;51:2778–86. [DOI] [PubMed]

39.

Fährrolfes R, Bietz S, Flachsenberg F, Meyder A, Nittinger E, Otto T, et al. ProteinsPlus: a web portal for structure analysis of macromolecules. Nucleic Acids Res. 2017;45:W337–43. [DOI] [PubMed] [PMC]

40.

Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, et al. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res. 2000;33:889–97. [DOI] [PubMed]

41.

Ado MA, Abas F, Mohammed AS, Ghazali HM. Anti- and pro-lipase activity of selected medicinal, herbal and aquatic plants, and structure elucidation of an anti-lipase compound. Molecules. 2013;18:14651–69. [DOI] [PubMed] [PMC]

42.

Sumarlin LO, Suprayogi A, Rahminiwati M, Satyaningtijas A, Nugraha AT, Sukandar D, et al. Identification of compounds flavonoids namnam leaf extract (Cynometra cauliflora) as inhibiting a-glucosidase. J Phys: Conf Ser. 2020;1594:012005. [DOI]

43.

Hiranrat W, Hiranrat A, Jaijong W. Flavones from the twigs of Cynometra cauliflora. Proceedings of the 5th International Conference on Natural Products for Health and Beauty (NATPRO 5); 2014 May 6-8; Phuket, Thailand. 2014. pp. 90–3.

44.

Guruge AG, Udawatte C, Weerasinghe S. An in silico approach of coumarin-derived inhibitors for human DNA topoisomerase I. Aust J Chem. 2016;69:1005–15. [DOI]

45.

Gohlke H, Hendlich M, Klebe G. Knowledge-based scoring function to predict protein-ligand interactions. J Mol Biol. 2000;295:337–56. [DOI] [PubMed]

46.

Chathurangi RPDD, Wathsara HPT, Samarakoon KW, Ranasinghe P, Dissanayake PK. Phytochemical screening and antioxidant activities of selected tropical underutilized fruits. Proceeding of the 2nd International Research Symposium; 2018 Feb 1-2; Badulla, Sri Lanka. 2018. p. 92.

47.

Sumarlin LO, Suprayogi A, Rahminiwati M, Satyaningtijas AS, Sukandar D, Tjachja A, et al. The ability of namnam (Cynometra cauliflora) leafs extract as antidiabetic agent through α–glucosidase inhibition on several extraction stages. IJSBAR. 2016;30:112–23.

48.

Wahab NZA, Badya N, Ibrahim N, Kamarudin MKA, Juahir H, Toriman ME. Antiviral activity of Cynometra cauliflora leaves methanolic extract towards dengue virus type 2. Int J Eng Technol. 2018;7:344–7.

49.

Wahab NZA, Badya N, Ibrahim N, Kamarudin MKA. Phytochemistry and antibacterial activity of Cynometra cauliflora. India J Public Health Res Dev. 2019;10:806–10.

50.

Ulpiyah Z, Shita ADP, Wahyukundari MA. Inhibition of namnam (Cynometra cauliflora L.) leaves extract on the growth of Porphyromonas gingivalis. Padjadjaran J Dent. 2019;31:106–11. [DOI]

51.

Ali SI, El-Baz FK, El-Emary GAE, Khan EA, Mohamed AA. HPLC-analysis of polyphenolic compounds and free radical scavenging activity of pomegranate fruit (Punica granatum L.). Int J Pharm Clin Res. 2014;6:348–55.

52.

Weerasekera AC, Samarasinghe K, de Zoysa HKS, Bamunuarachchige TC, Waisundara VY. Cinnamomum zeylanicum: morphology, antioxidant properties and bioactive compounds. In: Waisundara V, editor. Antioxidants - benefits, sources, mechanisms of action. Rijeka: IntechOpen; 2021. pp. 1–14. [DOI]

53.

Perera HDSM, Samarasekera JKRR, Handunnetti SM, Weerasena OVDSJ. In vitro anti-inflammatory and anti-oxidant activities of Sri Lankan medicinal plants. Ind Crops Prod. 2016;94:610–20. [DOI]

54.

Olech M, Nowak R, Załuski D, Kapusta I, Amarowicz R, Oleszek W. Hyaluronidase, acetylcholinesterase inhibiting potential, antioxidant activity, and LC-ESI-MS/MS analysis of polyphenolics of rose (Rosa rugosa Thunb.) teas and tinctures. Int J Food Prop. 2017;20:S16–25. [DOI]

55.

Tajudin TJSA, Mat N, Siti-Aishah AB, Yusran AAM, Alwi A, Ali AM. Cytotoxicity, antiproliferative effects, and apoptosis induction of methanolic extract of Cynometra cauliflora Linn. Whole fruit on human promyelocytic leukemia HL-60 cells. Evid Based Complement Alternat Med. 2012;2012:127373. [DOI] [PubMed] [PMC]

56.

Kraikruan W, Klaipook W, Thanumthat R. Benefits of local humid tropical fruit trees in Thailand. In: Somsri S, Chapman K, Sukhvibul N, Chantrasmi V, editors. International symposium on durian and other humid tropical fruits. Chantaburi: Acta Horticulturae; 2017. pp. 235–40. [DOI]