Exploring the Antimicrobial Mechanism of Morinda citrifolia: An Integrated Phytochemical and Molecular Docking Approach

Dr. Suresh V., Dr. Senthilkumar S.K., Jayaseelan K., Arunadevi L., Blessy Bavina V., Chandramouli S., Charumathi E., Deepa R.,

doi:10.5281/zenodo.17008835

Research Paper | Open Access
Volume 03 | Issue 08 | Article Id IJPS/250308360

Exploring the Antimicrobial Mechanism of Morinda citrifolia: An Integrated Phytochemical and Molecular Docking Approach
Dr. Suresh V.* Dr. Senthilkumar S.K. Jayaseelan K. Arunadevi L. Blessy Bavina V. Chandramouli S. Charumathi E. Deepa R.
Arunai College of Pharmacy, Tiruvannamalai, Tamilnadu, India

Abstract

The present study investigates the antimicrobial potential of Morinda citrifolia through in vitro evaluation and molecular docking. Antimicrobial assays revealed significant inhibitory activity against selected pathogenic microorganisms, indicating the presence of active phytoconstituents. Identified bioactive compounds were subjected to molecular docking against key bacterial target proteins, demonstrating strong binding affinities and potential inhibitory mechanisms. The combined results highlight M.citrifolia as a promising candidate for developing novel antimicrobial agents.

Keywords

Morinda citrifolia; antimicrobial mechanisms; molecular docking; phytoconstituents; bacterial target proteins

Introduction

An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat.

For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function.

Antimicrobial medicines to treat infection are known as antimicrobial chemotherapy, while antimicrobial drugs are used to prevent infection, which known as antimicrobial prophylaxis.

The main classes of antimicrobial agents are disinfectants (non-selective agents, such as bleach), which kill a wide range of microbes on surfaces to prevent the spread of illness, antiseptics which are applied to living tissue and help reduce infection during surgery, and antibiotics which destroy microorganisms within the body.

ANTIFUNGALS

Antifungals are used to kill or prevent further growth of fungi. In medicine, they are used as a treatment for infections such as athlete's foot, ringworm and thrush and work by exploiting differences between mammalian and fungal cells. Unlike bacteria, both fungi and humans are eukaryotes.

ANTIVIRAL

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics, specific antivirals are used for specific viruses. They should be distinguished from vermicides, which actively deactivate virus particles outside the body.

ANTIPARASITIC:

Antiparasitic are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminthes, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitic target the parasitic agents of the infections by destroying them or inhibiting their growth; they are usually effective against a limited number of parasites within a Particular class.

MECHANISM OF ACTION OF ANTI MICROBIALS:

1. Inhibition of Cell Wall Synthesis

Target: Peptidoglycan layer in bacterial cell walls
Effect: Weakens the cell wall, leading to cell lysis and death
Mainly active against: Gram-positive bacteria
Examples:
- β-lactams: Penicillins, Cephalosporins
- Glycopeptides: Vancomycin

2. Disruption of Cell Membrane Function

Target: Cell membrane (phospholipid or sterol components)
Effect: Destroys membrane integrity→leakage of vital molecules→cell death
Examples:
- Polymyxins (bacteria)
- Amphotericin B, Nystatin (fungi - target ergosterol)

3. Inhibition of Protein Synthesis

Target: Bacterial ribosomes (30S or 50S subunits)
Effect: Blocks protein production → inhibits growth or kills cell
Examples:
- Tetracyclines, Aminoglycosides (30S)
- Macrolides, Chloramphenicol (50S)

4. Inhibition of Nucleic Acid Synthesis

Target: Enzymes for DNA or RNA replication
Effect: Prevents DNA replication or transcription → halts cell division
Examples:
- Fluoroquinolones (inhibit DNA gyrase)
- Rifampin (inhibits RNA polymerase)

5. Inhibition of Essential Metabolic Pathways

Target: Enzymes in folic acid synthesis (used for DNA/RNA synthesis)
Effect: Starves the cell of critical nutrients
Examples:
- Sulfonamide
- Trimethoprim

PLANT PROFILE

NONI

Common name: Indian Mulberry, Great Morinda, Cheesefruit,

Scientific name: Morinda citrifolia

Family: Rubiaceae

Geographical Source : Kerala, Karnataka and Tamil Nadu

Scientific classification:

Kingdom : Plantae
Order : Gentianales
Family : Rubiaceae
Subfamily : Rubioideae
Genus : Morinda
Species : Morinda citrifolia

Vernacular names:

English : Indian Mulberry
Tamil : Nuna
Hindi : Bartundi
Telugu : Mogali
Kannada : Tagase maddi

Description:

Morinda citrifolia is a shrub or small tree up to 6 m tall, with grey-brown bark. The twigs are more or less square in cross-section and often fleshy. Stipules are present, very broad and obtuse at the apex, measuring up to 2 cm wide and long. The large glabrous leaves are elliptic to ovate in shape and have 6–9 pairs of lateral veins. The flowers are white and tubular with five lobes, measuring about 15 cm long and across.

The fruits are initially green, transitioning through pale yellow to white or grey, and when ripe they emit a pungent odour. They are irregularly ellipsoid or ovoid.

Chemical Constituent:

Morinda citrifolia fruit powder contains carbohydrates and dietary fibre in moderate amounts. These macronutrients reside in the fruit pulp, as M. citrifolia juice has sparse nutrient content. Morinda citrifolia fruit contains diverse phytochemicals, including anthraquinones, lignans, oligo- and polysaccharides, flavonoids, iridoids, such as deacetylasperulosidic acid, scopoletin , fatty acids, catechin, beta-sitosterol, damnacanthal, and alkaloids.

Pharmacological profile:

Antibacterial
Antiviral
Antifungal
Anthelminthic
Antitumor
Analgesic
Hypotensive
Anti-inflammatory
Immune-enhancing effect.

MOLECULAR DESIGN

Molecular design is the process of finding new medicines based on the knowledge of a biological target, it enabled the chemist to predict the structure and then it also allows the medicinal chemist to evaluate the interaction between a compound and its target site before synthesizing a compound so as to increase the ability by reducing the side effects. Various software used :

Chem Sketch
Mol inspiration
Swiss ADME
Pro Tox 3.0

MOL INSPIRATION

This software is used to calculate the following properties

Log P
Molecular weight
Number of H-bond donor
Number of H-bond acceptor
Number of rotatable bonds

In addition to “LIPINSKI’S RULE” another rule was proposed VEBER he states that the number of rotatable bonds should be less than 10. This rule is more appropriate for oral drug only. According to the veber’s rule

The Log P value should not be more than 5
The molecular weight of the compound should not more than 500
No. of H-bond donor not more than 5
No. of rotatable bonds should not be more than 10

3D STRUCTURAL VIEW OF COMPOUNDS

Morphine

Nicotine

Atropine

Quinine

Mescaline

Ephedrine

Caffeine

Theobromine

Solanine

Reserpine

Strychnine

Vincristine

Cocaine

Berberine

Pilocarpine

Senecionine

Quercetine

Kaempferol

Rutin

Gallic acid

Caffeic acid

Ursolic acid

Oleanolic acid

β-Sitosterol

Linalool

Geraniol

Tannic acid

Punicalaginn

Catechin

Epicatechin

Procyanidin

Deacetylsperulosidic acid

Asperulosidic acid

Ginsenosides

Glycyrrhizin

Dioscin

Tigogenin

Oleanane

Ursane

Dammarane

TABLE-1:PROPERTIES OF PHYTOCONSTITUENTS

Sr. No	PHYTOCONSIUENTS	PUBCHEM ID	MOLECULAR WEIGHT	MOLECULAR FORMULA
1	MORPHINE	5288826	285.34 g/mol	C₁₇H₁₉NO₃
2	NICOTINE	89594	162.34 g/mol	C₁₀H₁₄N₂
3	ATROPINE	174174	289.4 g/mol	C₁₇H₂₃NO₃
4	QUININE	6999115	325.4 g/mol	C₂₀H₂₅N₂O₂
5	MESCALINE	4075	153.14 g/mol	C₇H_7NNO₃
6	EPHEDRINE	9457	165.23 g/mol	C₁₀H₁₅NO
7	CAFFINE	2519	194.19 g/mol	C₈H₁₀N₄0₂
8	THEOBROMINE	5429	180.16 g/mol	C₇H₈N₄O₂
9	SOLANINE	30185	868.1 g/mol	C₄₅H₇₃NO₁₅
10	RESERPINE	5770	608.7 g/mol	C₃₃H₄₀N₂0₉
11	STRYCHNINE	441071	334.4 g/mol	C₂₁H₂₂N₂O₂
12	VINCRISTINE	5978	825.0 g/mol	C₄₅H₅₆N₄O₁₀
13	COCAINE	446220	303.34 g/mol	C₁₇H₂₁NO₄
14	BERBERINE	2353	336.4 g/mol	C₂₀H₁₈NO₄⁺
15	PILOCARPINE	5910	208.26 g/mol	C₁₁H₁₆N₂O₂
16	SENECIONINE	5280906	335.4 g/mol	C₁₈H₂₅NO₅
17	QUERCETINE	5280343	302.23 g/mol	C₁₅H₁₀O₇
18	KAEMPFEROL	5280863	286.24 g/mol	C₁₅H₁₀O₆
19	RUTIN	6728944	610.5 g/mol	C₂₇H₃₀O₁₆
20	GALLIC ACID	370	170.12g/mol	C₇H₆O₅
21	CAFFEIC ACID	689043	180.16g/mol	C₉H₈O₄
22	URSOLIC ACID	64945	456.7g/mol	C₃₀H₄₈O₃
23	OLEANOLIC ACID	10494	456.7g/mol	C₃₀H₄₈O₃
24	β-SITOSTEROL	222284	414.7g/mol	C₂₉H₅₀O
25	LINALOOL	6549	154.25g/mol	C₁₀H₁₈O
26	GERANIOL	637566	0.25g/mol	C₁₀H₁₈O
27	TANNIC ACID	16129778	1701.2g/mol	C₇₆H₅₂O₄₆
28	PUNICALAGIN	16129719	1084.7g/mol	C₄₈H₂₈O₃₀
29	CATECHIN	9064	290.27g/mol	C₁₅H₁₄O₆
30	EPICATECHIN	72276	290.27g/mol	C₁₅H₁₄O₆
31	PROCYANIDIN	107876	594.5g/mol	C₃₀H₂₆O₁₃
32	DEACETYLASPERULOSIDIC ACID(DAA)	12315350	390.34g/mol	C₁₆H₂₂O₁₁
33	ASPERULOSIDIC ACID (AA)	119688	432.4g/mol	C₁₈H₂₄O₁₂
34	GINSENOSIDES	3086007	444.7g/mol	C₁₈H₅₂O₂
35	GLYCYRRHIZIN	14982	822.9 g/mol	C₄₂H₆₂O₁₆
36	DIOSCIN	119245	869.0 g/mol	C₄₅H₇₂O₆
37	TIGOGENIN	99516	416.6 g/mol	C₂₇H₄₄O₃
38	OLEANANE	9548717	412.27 g/mol	C₅₆H₉₂O₂₉
39	URSANE	9548870	412.7 g/mol	C₃₀H₅₂
40	DAMMARANE	9548714	414.7 g/mol	C₃₀H₅₄

TABLE-2: ADME PROPERTIES OF PHYTOCONSTITUENTS:

Sr. No.	Phytoconsttiuents	Number Of Rota- Table Bonds	Number Of Bond Acceptor	Number Of Bond Donor	Lpgpc/ W9 (Liogl)	Molar Refractive	Solu- Bility	Gastro- Intestinal Absorption
1	MORPHINE	0	4	2	2.55	32.27	SOLUBLE	HIGH
2	NICOTINE	1	2	0	2.04	53.13	SOLUBLE	HIGH
3	ATROPINE	5	4	1	2.79	84.51	SOLUBLE	HIGH
4	QUININE	4	4	1	3.36	99.73	SOLUBLE	HIGH
5	MESCALINE	5	4	1	2.37	53.40	SOLUBLE	HIGH
6	EPHEDRINE	3	2	2	2.16	49.79	SOLUBLE	HIGH
7	CAFFINE	0	3	0	1.79	52.04	SOLUBLE	HIGH
8	THEOBROMINE	0	3	1	1.22	47.14	SOLUBLE	HIGH
9	SOLANINE	6	12	7	2.90	190.96	SOLUBLE	LOW
10	RESERPINE	10	10	1	5.21	165.52	SOLUBLE	HIGH
11	STRYCHNINE	0	3	0	2.78	101.05	SOLUBLE	HIGH
12	VINCRISTINE	11	12	3	4.70	233.11	SOLUBLE	LOW
13	COCAINE	5	5	0	3.22	54.85	SOLUBLE	HIGH
14	BERBERINE	2	4	0	0.00	94.87	SOLUBLE	HIGH
15	PILOCARPINE	3	3	0	1.81	56.47	SOLUBLE	HIGH
16	SENECIONINE	0	6	1	2.43	91.93	SOLUBLE	HIGH
17	QUERCETINE	1	7	5	1.63	78.03	SOLUBLE	HIGH
18	KAEMPFEROL	1	6	4	1.70	76.01	SOLUBLE	HIGH
19	RUTIN	6	16	10	0.46	141.38	SOLUBLE	LOW
20	GALLIC ACID	1	5	4	0.21	39.47	SOLUBLE	HIGH
21	CAFFEIC ACID	2	4	3	0.97	47.16	SOLUBLE	HIGH
22	URSOLIC ACID	1	3	2	3.95	136.91	SOLUBLE	LOW
23	OLEANOLIC ACID	1	3	2	3.94	136.65	SOLUBLE	LOW
24	Β-SITOSTEROL	6	1	1	5.05	133.23	SOLUBLE	LOW
25	LINALOOL	4	1	1	2.70	50.44	SOLUBLE	HIGH
26	GERANIOL	4	1	1	2.52	50.40	SOLUBLE	HIGH
27	TANNIC ACID	10	19	11	0.36	142.56	SOLUBLE	LOW
28	PUNICALAGIN	2	30	17	0.42	252.09	SOLUBLE	LOW
29	CATECHIN	1	6	5	1.33	74.33	SOLUBLE	HIGH
30	EPICATECHIN	1	6	5	1.47	74.33	SOLUBLE	HIGH
31	PROCYANIDIN	4	13	10	2.17	147.52	SOLUBLE	LOW
32	DEACETYLASPERULOSIDIC ACID(DAA)	5	11	7	0.58	83.73	SOLUBLE	LOW
33	ASPERULOSIDIC ACID (AA)	7	12	6	1.13	93.47	SOLUBLE	LOW
34	GINSENOSIDES	4	2	2	5.01	138.72	SOLUBLE	LOW
35	GLYCYRRHIZIN	7	16	8	1.89	202.84	SOLUBLE	LOW
36	DIOSCIN	0	3	0	2.37	00.40	SOLUBLE	HIGH
37	TIGOGENIN	7	13	1	4.53	122.07	SOLUBLE	HIGH
38	OLEANANE	0	0	0	5.05	134.19	SOLUBLE	LOW
39	URSANE	0	0	0	5.02	134.45	SOLUBLE	LOW
40	DAMMARANE	5	0	0	5.61	136.83	SOLUBLE	LOW

TABLE-3: TOXICITY STUDY OF PHYTOCONSTITUENTS

Sr. No	Phyto Constituents	Nephro Toxicity	Carcino Toxicity	Cardio Toxicity	Muta Genecity	Cyto Toxicity	Bbb-Barrier	Nutritional Toxicity	Aryl Hydrocarbon Receptor	Androgen Receptor
1	Morphine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
2	Nicotine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
3	Atropine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
4	Quinine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
5	Mescaline	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
6	Ephedrine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
7	Caffeine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
8	Theo-Bromine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
9	Solanine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
10	Reserpine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
11	Strychinine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
12	VinCristine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
13	Cocaine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
14	Berberine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
15	Pilocarpine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
16	Senecionine	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
17	Quercetin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
18	Kaempferol	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
19	Rutin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
20	Gallic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
21	Caffeic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
22	Ursolic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
23	Oleanolic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
24	Β-sitosterol	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
25	Linalool	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
26	Geraniol	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
27	Tannic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
28	Punicalagin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
29	Catechin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
30	Epicatechin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
31	Procyanidin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
32	Deacetyl Asperuloidic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
33	Asperulo Sidic Acid	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
34	Ginseno Sides	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
35	Glycyrrhzin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
36	Dioscin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
37	Tigogenin	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
38	Oleanane	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
39	Ursane	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive
40	Dammarane	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive	Inactive

ANTI MICROBIAL ACTIVITY

PREPARATION OF PROTEIN:

The protein target, obtained from the RCSB protein data bank with the PDB accession. Code 1ULK function as docking receptor. The active site of the receptor was cleared of all sound ligands and water molecules.

CRYSTAL STRUCTURE OF 1ULK

PDB DOI: https://doi.org/10.2210/pdb1ULK/pdb

Classification: SUGAR BINDING PROTEIN

Organism(s): Phytolacca americana

Mutation(s): No

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.203 (Depositor)
R-Value Work: 0.176 (Depositor)
R-Value Observed: 0.176 (Depositor)

PREPARATION OF PROTEIN:

The protein target, obtained from the RCSB protein data bank with the PDB accession. Code 6YIS function as docking receptor. The active site of the receptor was cleared of all sound ligands and water molecules.

CRYSTAL STRUCTURE OF 6YIS

PDB DOI: https://doi.org/10.2210/pdb6YIS/pdb

Classification: HYDROLASE

Organism(s): Bos taurus

Mutation(s): No

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.19 Å
R-Value Free: 0.173 (Depositor), 0.170 (DCC)
R-Value Work:0.150 (Depositor), 0.150 (DCC)
R-Value Observed: 0.151 (Depositor)

TABLE-4: BINDING AFFINITY OF PHYTOCONSTITUENTS USING

Sr. No.	Phytoconsiuents	Binding Affinity
1	Morphine	-7.0219
2	Nicotine	-5.9739
3	Atropine	-7.3454
4	Quinine	-7.1117
5	Mescaline	-6.3483
6	Ephedrine	-6.3880
7	Caffine	-6.5242
8	Theobromine	-7.8453
9	Solanine	-8.7729
10	Reserpine	-8.7729
11	Strychnine	-6.7014
12	Vincristine	-8.6114
13	Cocaine	-7.3386
14	Berberine	-6.7822
15	Pilocarpine	-6.8946
16	Senecionine	-6.5852
17	Quercetine	-6.6996
18	Kaempferol	-7.6110
19	Rutin	-8.4362
20	Gallic Acid	-5.9175
21	Caffeic Acid	-6.6113
22	Ursolic Acid	-7.1021
23	Oleanolic Acid	-7.0433
24	Β-Sitosterol	-7.2657
25	Linalool	-6.1516
26	Geraniol	-6.4432
27	Tannic Acid	-8.9826
28	Punicalagin	-7.9427
29	Catechin	-6.4530
30	Epicatechin	-7.1191
31	Procyanidin	-8.1106
32	Deacetylasperulosidic Acid(Daa)	-7.2467
33	Asperulosidic Acid (Aa)	-7.4013
34	Ginsenosides	-7.3768
35	Glycyrrhizin	-8.0319
36	Dioscin	-9.2254
37	Tigogenin	-7.2500
38	Oleanane	-6.9805
39	Ursane	-7.1507
40	Dammarane	-7.2525

RESULTS AND CONCLUSION

The present investigation focused on the antimicrobial potential of Morinda citrifolia, combining antimicrobial evaluation with in-silico molecular docking studies. The study systematically screened phytoconstituents, assessed their ADME properties, binding affinities with selected microbial target proteins, and evaluated their toxicity profiles.

Results

Antimicrobial assays of M. citrifolia revealed significant inhibitory effects against a range of pathogenic microorganisms, suggesting the presence of bioactive secondary metabolites. Phytochemical analysis confirmed the occurrence of diverse compounds including alkaloids, flavonoids, iridoids, phenolics, terpenoids, and sterols, many of which are well-documented for antimicrobial and pharmacological effects.

A total of 40 phytoconstituents were subjected to computational screening. ADME analysis highlighted that most compounds exhibited favorable physicochemical properties under Lipinski’s Rule of Five and Veber’s Rule, confirming their potential oral bioavailability. However, some larger molecules (such as tannic acid, punicalagin, and glycyrrhizin) showed reduced gastrointestinal absorption, indicating possible limitations in systemic bioavailability.

Molecular docking studies were performed using 1ULK (sugar-binding protein) and 6YIS (hydrolase protein) as bacterial target proteins. Binding affinity scores demonstrated strong interactions of several phytochemicals. Notably, Dioscin (-9.2254 kcal/mol), Tannic acid (-8.9826 kcal/mol), Solanine (-8.7729 kcal/mol), Reserpine (-8.7729 kcal/mol), and Vincristine (-8.6114 kcal/mol) exhibited the most favorable docking energies, surpassing several standard antimicrobial agents. Flavonoids such as quercetin, kaempferol, and rutin also displayed promising affinities, reinforcing their role as natural antimicrobial scaffolds.

Toxicity prediction studies indicated that all tested compounds were non-toxic across nephrotoxicity, cardiotoxicity, genotoxicity, and mutagenicity assays. Importantly, none showed significant nutritional or blood–brain barrier toxicity risks, which enhances their therapeutic relevance. This combination of potent binding affinity, favorable ADME properties, and low predicted toxicity suggests that multiple phytoconstituents from M. citrifolia could act as promising antimicrobial drug leads.

CONCLUSION

This study highlights the strong antimicrobial efficacy of Morinda citrifolia, supported by both experimental assays and molecular docking simulations. Key bioactive compounds, including Dioscin, Tannic acid, Solanine, Reserpine, and Rutin, exhibited notable binding affinities with bacterial proteins, indicating their potential as natural inhibitors of microbial growth. Computational ADME and toxicity assessments further confirmed that several of these phytoconstituents possess favorable drug-like properties with minimal safety concerns.

The results establish M. citrifolia as a valuable source of antimicrobial phytochemicals with the potential to serve as lead molecules in developing new therapeutic agents. In the context of rising antimicrobial resistance, such naturally derived compounds represent sustainable and safer alternatives to conventional antibiotics. The integration of in vitro assays with in silico modeling provides deeper insight into mechanisms of action, while also streamlining the identification of promising candidates.

Future directions should focus on in vivo validation of these compounds, structural optimization to enhance bioactivity, and studies on synergistic effects with existing antibiotics to improve clinical outcomes. Collectively, the findings reinforce the medicinal value of M. citrifolia and its promise in next-generation antimicrobial drug discovery.

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