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. 2024 Jul 19;12(2):67. doi: 10.1007/s40203-024-00240-1

Drug-likeness analysis, in silico ADMET profiling of compounds in Kedrostis foetidissima (Jacq.) Cogn, and antibacterial activity of the plant extract

Kommidi Saritha 1,✉, Munagala Alivelu 2, Mustafa Mohammad 3
PMCID: PMC11264488  PMID: 39050777

Abstract

Plants are a treasure trove of bioactive compounds. Kedrostis foetidissima (Jacq.) Cogn. has many important phytoconstituents like cucurbitacins, rutin, and quercitin compounds. Among these compounds, Quercetin-3-O- Rhamnoside (1) has antioxidant, anti-inflammatory, anticancer properties. Rutin (2) has anti-inflammatory, antioxidant, anti-diabetic, anti-microbial, antiviral properties, 7, 10—Hexa decadienoic acid methyl ester (3) has anti-inflammatory, antioxidant, hypocholesterolemia and anticancer activities. Docosanoic acid (4) has antioxidant, α-Glucosidase inhibitory activity. 3,7,11,15-Tetra methyl hexa decan-1-ol (5) has antiviral properties. Cucurbitacin-B (6) has antipyretic, analgesic, anti-inflammatory, antimicrobial, and antitumor activities. Performance of experimental studies on phytochemicals become more difficult as the availability of compounds in small quantities, hence the computational methods becomes important for drug discovery. Based on their biological activity, compounds 1–6 were tested for in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and drug-likeness properties using the Swiss ADME online web server and the pkCSM server. All the studied compounds obey Lipinski's rule of five except compounds 1 and 2 with two and three violations each. The entire selected compounds have a good bioavailability score in the recommended range of 0 to 1. Compound 4 has high (0.85) and compounds 1 and 2 have low (0.17) oral bioavailability scores. All the selected compounds from Kedrostis foetidissima have strong pharmacological activities. Supporting this, the selected plant methanol extracts of leaf, stem callus, and tuber have shown well in vitro antibacterial activity against Bacillus subtilis, Escherichia coli, and Proteus vulgaris. Therefore, these compounds may be developed into drug molecules with additional clinical research.

Keywords: Kedrostis foetidissima, ADMET, Antibacterial, In-silico

Introduction

Kedrostis foetidissima (Jacq.) Cogn is an important medicinal plant belonging to the Cucurbitaceae family. Kedrostis foetidissima is a climber in the family. It is a monoecious scandent shrub with a perennial rootstock that grows up to a height of 2 m. There are about 27 species in Kedrostis (Chakrvarty 1982). It is rich in regions of South Africa, Asia, India to Burma (John 2019). In India, it is distributed in warm and dry areas of Gujarat, Karnataka, Madhya Pradesh, Maharashtra, Tamil Nadu, and Andhra Pradesh (erstwhile). Kedrostis foetidissima had great medicinal value and uses in traditional and folklore systems of medicine (Siddha) for many years. This plant is used for curing various ailments such as cough, common cold, and measles, healing wounds, and treating bloats in cattle (Amutha 2017). It is also used for eczema, diarrhea in boils (https//www.wildturmeric.net), Asthma (Dogra et al. 2015), and hypertension and stomach-ache (Mugomeri et al. 2016).

Preliminary phytochemical analysis showed the presence of alkaloids, flavonoids, glycosides, phenols, saponins, steroids, and triterpenoids (Thenmozhi et al. 2014). GC–MS analysis of leaf extracts revealed 7,10-hexadecadienoic methyl ester, 2-hexadecen-1-ol, 3,7,11,15 Tetramethyl hexa decan-1 -ol, 1 H-1,2,4-triazole-3,5-dicarbaldehyde, and docosanoic acid as major components (Kalaisezhiyen and Sasikumar 2012). Phytochemical analysis of this plant through column chromatography revealed the presence of compounds like rutin, quercetin-o-rhamnoside, and cucurbitacin glycoside (Amutha 2017). The more interesting feature of this plant is the presence of cucurbitacins. Cucurbitacins B, D, E, and I were reported in this plant (Rios et al. 2005). Cucurbitacin C from stems and I from leaves were reported (Njoroge and Newton 1994 Jul).

Kedrostis foetidissima leaf extract showed anti-bacterial and antifungal activity (Priyavardhini et al. 2008, 2012), antidiarrheal activity (Sivaprakash 2016), antioxidant activity (Pavithra and Saravanan 2019), antiplasmodial, antileishmanial, and antitrypanosomal activity (Mothana et al. 2014), and wound healing property. Leaf, stem, and fruit extracts of this plant showed anticancer and anti-proliferative activity against human hepatocellular liver carcinoma cell lines (HEPG2), ethanol extracts, silver, and gold nanoparticles against the human osteosarcoma cell lines (MG-63), lung cancer cell lines A-549, and breast cancer cell lines MCF-7 and YMB-1 (Choene and Motadi 2012).

Drug development involves the assessment of the absorption, distribution, metabolism, and excretion (ADME) of a compound. Drug-likeness described as a complex balance of various molecular properties and structural features that can explain whether a compound is similar to the known drugs (Daina et al. 2017). Drug-likeness was evaluated by the Lipinski rule of five, which evaluates five simple physicochemical parameters. The performance of experimental studies becomes more difficult with the availability of compounds for physio-chemical screening in small quantities and using non-traditional techniques; hence, computational methods become important for drug discovery (Lipinski et al. 2001). Lipinski’s rule of five (RO5) was major in drug discovery. This rule used to determine the bioavailability of bulk materials to inspect their drug-like properties (Kavitha and Alivelu 2021).

An ideal drug administered orally has been absorbed from the gastrointestinal tract, distributed to its specific target, metabolized in the body without altering its properties, and excreted without any damage, or causing toxicity (Khan et al. 2017). Predictive tools for accessing the pharmacokinetic and toxicological properties, and the pharmacodynamic properties, are crucial for the early developmental stages of drug discovery processes. In silico methods are employed to estimate ADMET properties because in vivo and in vitro evaluations are becoming premium and laborious (Cheng et al. 2013).

Flavonoids are specialized metabolic compounds that possess antimicrobial properties, which include anti-viral activity (Rahman et al. 2021), antioxidants, and antidiabetic (Liu 2016). and anticancer activities (Raffa et al. 2017). Rutin and quercetin are flavonoid compounds. Which possess antiviral, antibacterial, anti-inflammatory, antioxidant, hepatoprotective, and anticancer activities (Gullón et al. 2017). Cucurbitacins are highly oxidized tetracyclic triterpenoids that are often present in the Cucurbitaceae family and have strong anticancer activity and antiviral, antibacterial, anti-hypertensive, anti-hyperglycemic, and anti-parasitic activities. They are also used in central nervous system disorders (Cai et al. 2015). Cucubitacin-B shows anticancer activity against the human leukemia cell line 562 (Chan et al. 2010), colorectal cancer cells (Chai et al. 2018), primary effusion lymphoma (PEL) (Ueno et al. 2021), and hepatocellular carcinoma cell line BEL-7402. 7, 10-hexa deca dienoic acid is an omega-6 fatty acid that has antioxidant, anti-inflammatory, hypocholesterolemic, and anti-cancer activities (Alqahtani et al. 2019). Docosanoic acid possesses antioxidant and α-glucosidase inhibitory activity (Zhang et al. 2020), 3,7,11,15-Tetramethyl-1-hexadecanol has antiviral properties (Sangeetha et al. 2017). Different biological activities are possessed by the Kedrostis foetidissima compounds that were chosen for drug-likeness analysis and ADMET profiling. Plant methanol and aqueous extracts of leaves, stem callus, and tubers have been investigated for them in vitro antibacterial activity against Proteus vulgaris, Escherichia coli, and Bacillus subtilis to substantiate this.

Materials and methods

Computational method

The structures of the biologically active compounds present in Kedrostis foetidissima were identified from the literature. Six compounds (Fig. 1) are selected for drug-likeness analysis and ADMET studies. They are Quercetin-3-O- Rhamnoside (1), Rutin (2), 7, 10—Hexa decadienoic acid methyl ester (3), Docosanoic acid (4), 3,7,11,15-Tetra methyl hexa decan-1-ol (5), and Cucurbitacin-B (6).

Fig. 1.

Fig. 1

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Structures of selected compounds of Kedrostis foetidissima

The Swiss ADME online web server (http://www.swissadme.ch/) is used to predict the drug-likeness properties and oral bioavailability of selected compounds. As per Lipinski’s rule of five (RO5), a drug-like compound should have a molecular weight (MW) ≤ 500 Da, Van der Walls topological polar surface area (TPSA) value of ≤ 120 A°, a hydrogen bond acceptor (HBAs) ≤ 10, a hydrogen bond donor (HBD’s) ≤ 5, a partition coefficient (log P) ≤ 5, and only one violation allowed. The bioavailability of selected compounds was analysed by the bioavailability RADAR. For each of the selected compounds, several pharmacokinetic parameters for absorption, distribution, metabolism, excretion, and toxicity (ADMET) were analyzed using the pkCSM server (Pires et al. 2015).

Antibacterial studies

Plant material

Kedrostis foetidissima plant material (tubers) was collected in the rainy season (July) from Hanumakonda district. The collected tubers were planted in the botanical garden of the Department of Botany, Kakatiya University, Hanumakonda. The plant material was authenticated by Dr. Mohammad Mustafa, Department of Botany, Kakatiya University, and Hanumakonda. Matured plant material is used for antimicrobial studies (Fig. 2a, b, c, and d).

Fig. 2.

Fig. 2

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a Plant stem meterial of Kedrostis foetidissima. b Plant tuber material of Kedrostis foetidissima. c Stem callus material of Kedrostis foetidissima. d Dried powders of tuber, stem and stem callus of Kedrostis foetidissima

Test microorganisms

The following three bacterial strains were received from the Dept. of Microbiology, Pingle Govt. College for Women (A), Hanumakonda, Telangana. They were maintained on agar slants in an incubator until the experiment. They are Gram-positive bacteria: Bacillus subtilis, Gram-negative bacteria: Escherichia coli, and Proteus vulgaris.

Nutrient media

Nutrient agar media prepared by using 15% agar, 5% peptone, 3% beef extract, and 3 gr. NaCl dissolved in 1L distilled water and sterilized by autoclaving. 15 ml of nutrient agar media was poured into Petri dishes (15 mm) to prepare agar test plates.

Materials and instruments

All of the chemicals and reagents used in this study are purchased from HiMedia Laboratories Private Limited Bioscience Company, India. The instruments used in the study are Autoclave (Indosurgicals-India), Laminar-air-flow (Bionics scientific- India), and Incubator (Bionics scientific- India).

Preparation of plant extract

About 100 g of shade-dried plant parts, like the stem, stem callus, and tuber of the experimental plant, were ground in a mortar and pestle to make a fine powder. These were extracted using methanol and aqueous solvents. Used the cold extraction method by continuously shaking plant material in solvent for 24 h. Then the solvent was filtered, and the filtrate was evaporated until it became semisolid. The extract was taken from plates and stored at 4 °C until use.

Agar-well diffusion method

Bacterial cultures were mixed with nutrient agar media when it was warm and in a melted state, and about 15 ml of media was poured into the Petri plates. Then the plates were closed and allowed to cool. After inoculation, wells were prepared with a 6 mm sterile cork borer. To the wells, 20 μl of plant extract solution was added by using a micropipette (Valgas et al. 2007). The test solution was prepared by dissolving the plant extract in dimethyl sulfoxide (DMSO). The plates were labeled, covered, inverted, and incubated in an incubator for 24 h. After that, the zone of inhibition was measured, and data were recorded. Mean of three replicates were taken.

Result and discussion

Drug-likeness and oral bioavailability analysis

The Swiss ADME tool (http://www.swissadme.ch/) was used to evaluate the drug-likeness properties and oral bioavailability of selected compounds from Kedrostis foetidissima. The obtained results are presented in Table 1. Lipinski’s rule of five (RO5) was major in drug discovery. All the studied compounds obey Lipinski's rule of five, except Compounds 1 and 2. It indicates that all the studied compounds can be easily carried away, diffused, and absorbed (Murugesan et al. 2020). Compound 1 violates the rule with 2 violations, i.e., HBA 11 and TPSA 269.43, and Compound 2 violates the rule with 3 violations, i.e., MW 620.25, HBA 16, and TPSA 190.28. Even though Compounds 1 and 2 violate Lipinski’s rule, a literature review revealed that two of the important limitations of Lipinski’s rule of five are that they exclude natural products and exaggerate oral bioavailability. Approximately 50% of the FDA-approved drugs in small compounds are known to either violate Lipinski’s rule or not be administered orally. Strictly Following these rules would lead to the overlooking of important lead compounds (Zhang and Wilkinson 2007). Hence, Compound 2 (Rutin) was considered a prospective lead molecule against SARS-CoV-2 (Zackria et al. 2022).

Table 1.

Drug likeness and oral bioavailability of selected compounds

Compound MW
(mg)		 HBD HBA Nnor TPSA Fraction Csp3 Log S (ESOL) Log P (XlogP3) RO5
Violations		 Bio availability score
1 448.38 7 11 3 269.43 0.29 − 3.33 0.86 2 0.17
2 610.25 10 16 16 190.28 0.44 − 3.3 − 0.33 3 0.17
3 266.42 0 2 13 26.3 0.71 − 4.25 5.74 1 0.55
4 340.58 1 2 20 37.3 0.95 − 7.16 10.37 1 0.85
5 125.9 1 4 2 75.71 0 − 0.63 − 0.42 0 0.55
6 558.708 3 8 6 138.20 0.75 − 4.57 2.64 1 0.55
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MW molecular weight, HBD no. of hydrogen bond donors, HBA no. of hydrogen bond acceptor, Nnor no. of rotatable bonds, TPSA topological polar surface area, Fraction Csp3 ratio of sp3 hybridized carbons over the total carbon count of the molecule, Log S water solubility, Log P logarithm of compound partition coefficient between n-octanol and water

Various properties for oral bioavailability (size, polarity, insolubility, instauration, flexibility, and lipophilicity) of the compounds were analyzed by comparing the radar plots (Fig. 3). The pink area in the RADAR shows the most favourable zone for each of the bioavailability (Abdul-Hammed et al. 2022). Except for Compounds 2 and 6, all are in the recommended SIZE < 500 mg/compound. Polarity (POLAR) was assessed by the TPSA, and all the compounds except compounds 1, 2, and 6 were within the limit, i.e., 120 A°, which implies that compounds are fulfilling the optimal requirement for drug absorption and are following the Lipinski rule. Lipophilicity (LIPO) and insolubility (INSOLU) are one of the important criteria for bioavailability studies. All the compounds except compound 4 are in the recommended range of ESOL log S. This compound shows a 7.16 value of ESOL log S, which means it is poorly soluble. Poor aqueous solubility and a slow dissipation rate can lead to poor oral absorption and lower oral bioavailability (Waterbeemd and Gifford 2003). So it can be administered through an oral or parenteral route (Sepay et al. 2021). The value of FLEX (Flexibility) is evaluated using the number of rotatable bonds, which does not exceed 9. For this character, except compounds 3, 4, and 5, all are accepting this. The instauration (INSATU) was determined using Fraction Csp3. All the selected compounds also obey this property. The entire selected compounds have a good bioavailability score (Fig. 4) in the recommended range of 0 to 1 (Martin 2005), hence they can be used for drug development.

Fig. 3.

Fig. 3

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The bioavailability RADAR for the selected compounds

Fig. 4.

Fig. 4

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Comparison of bioavailability score of selected molecules of Kedrostis foetidissima

In silico ADMET profiling of selected compounds

The results for ADMET profiling of selected compounds retrieved from the pkCSM server (https://biosig.lab.uq.edu.au/pkcsm/prediction) are presented in Table 2. The pharmacokinetics of a drug or compound help us know about the metabolism and movement of a drug in the body.

Table 2.

The results of ADMET profiling given by PkCSM server

Property Model name Unit Predicted values for compounds
1 2 3 4 5 6
Absorption Water solubility Numeric(log mol/L) − 2.903 − 2.892 − 6.166 − 7.584 − 6.67 − 5.149
CaCO3 permeability Numeric(log Papp in 10−6 cm/s) 0.048 − 0.949 1.072 1.513 1.614 − 0.124
Human intestinal absorption

Numeric

(% absorbed)

 52.709 23.446 89.942 90.785 93.347 76.76
Skin permeability Numeric( log Kp) − 2.735 − 2.735 − 2.734 − 2.625 − 2.457 − 3.315
P-glycoprotein substrate Categorical(yes/no) Yes Yes No No No Yes
P-glycoprotein inhibitor-I Categorical(yes/no) No No No No No Yes
P-glycoprotein inhibitor-II Categorical(yes/no) No No Yes Yes No Yes
Distribution VDss (human) Numeric(log L/kg) 1.517 1.663 − 0.554 0.468 0.277 − 0.105
Fraction unbound (human) Numeric( Fu) 0.13 0.187 0.009 0.502 0.079 0.221
BBB permeability Numeric (log BB) − 1.495 − 1.899 − 0.363 0.829 0.079 − 1.207
CNS permeability Numeric (log PS) − 4.156 − 5.178 − 1.488 − 1.62 − 1.572 − 3.279
Metabolism CYP2D6 substrate Categorical(yes/no) No No No No No No
CYP3A4 substrate Categorical(yes/no) No No Yes Yes Yes Yes
CYP1A2 inhibitor Categorical(yes/no) No No Yes Yes Yes No
CYP2C19 inhibitor Categorical(yes/no) No No No No No No
CYP2C9 inhibitor Categorical(yes/no) No No No No No No
CYP2D6 inhibitor Categorical(yes/no) No No No No No No
CYP3A4 inhibitor Categorical(yes/no) No No No No No No
Excretion Total clearance Numeric (log ml/min/kg) 0.364 − 0.369 1.967 1.616 1.968 0.093
Renal OCT2 substrate Categorical(yes/no) No No No No No No
Toxicity AMES toxicity Categorical(yes/no) No No No No No No
Max. Tolerated dose (human) Numeric( log mg/kg/day) 0.495 0.452 − 0.796 0.184 0.073 − 0.863
hERG I inhibitor Categorical(yes/no) No No No No No No
hERG II inhibitor Categorical(yes/no) No Yes No Yes No Yes
Oral acute rat toxicity (LD50) Numeric(mol/kg) 2.586 2.491 1.369 1.607 1.579 2.185
Oral chronic rat toxicity (LOAEL) Numeric (log mg/g bw/day) 3.022 3.673 3.639 1.009 2.854 1.687
Hepatotoxicity Categorical(yes/no) No No Yes No No No
Skin sensitisation Categorical(yes/no) No No Yes Yes Yes No
T. pyriformis toxicity Numeric(log ug/L) 0.285 0.285 0.381 1.829 2.061 0.316
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Absorption of the compounds is predicted using parameters like water solubility, CaCO3 permeability, skin permeability, and a P-gp inhibitor or substrate. All the selected compounds except compounds 3, 4, and 5 are within the range of log S, which is water solubility. CaCO3 permeability > 0.9 indicates high permeability. Compounds 3, 4, and 5 show higher CaCO3 permeability than all other compounds. Skin permeability (log Kp) > − 2.5 is considered to have low skin permeability for compounds. Except for compound 5, all are showing good skin permeability. Human intestinal absorption (HIA) value < 30% is considered to be a low absorption rate. An HIA value of 70 to 100% shows good intestinal absorption. Except for compound 2, all are showing excellent absorption. The main function of P-glycoprotein is to act as a biological barrier to eliminate toxins and xenobiotics from cells (Flores-Holguín et al. 2021). Hence, only compounds 1 and 2 are substrates for P-glycoprotein. None of the compounds is an inhibitor of P-Glycoprotein-I. Only compounds 3 and 4 are inhibitors of P-glycoprotein-II.

Among the distribution parameters, VDss (Volume of distribution at steady state), blood–brain barrier (BBB), CNS (Central nervous system) permeability, and fraction unbound (human) are calculated. The structural and physicochemical properties of the compound determine the distribution rate in the body. Some drugs may cross the blood–brain barrier (BBB) and enter the brain and central nervous system. Finally, the drug will bind to its molecular target. VDss calculates that the total dose of the drug would need to be uniformly distributed in blood plasma. Except for compounds 3 and 6, all have high VDss > 0.45, which indicates all these compounds readily distribute in blood plasma. For the selected compounds, all cannot cross the BBB, except compound 5, which is showing poor distribution in the brain. This means they don’t show any side effects on the brain. For the CNS, except compound 3, 4, and 5, all are showing less permeability to the brain.

The metabolism of drugs is carried out by cytochrome P450 enzymes. Inhibition of these enzymes leads to an increase in the concentration of drugs in the blood and shows adverse effects on organs. Among all the CYPs, CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP2C8 contribute over 50% of CYP-related drug metabolism (Zhao et al. 2021). For the metabolism parameters, compounds 3, 4, 5, and 6 are substrates for CYP3A4. Except for compounds 3, 4, and 5, all are inhibitors of CYP1A2, and the remaining compounds are non-inhibitors. All the compounds are non-inhibitors for CYP2AC19, CYP2AC9, CYP2D6, and CYP3A4. The inhibition of cytochrome proteins reduces the capacity and pharmacological effects of the drug (Kavitha et al. 2022). Hence, all studied compounds can metabolize excellently.

Excretion parameters include: Total clearance and renal OCT2 substrates were analyzed. Hydrophobicity and molecular weight of the compounds are the main criteria for drug elimination. For this, none of the compounds are substrates for all the renal OCT2. Except for compound 2, all the compounds showed a high (> 0.3) value of total clearance.

The AMES test (Salmonella mutagenicity assay) is a bacteria-based method to determine a compound’s mutagenic potential. When the test is positive, it shows that the substance is mutagenic and able to cause cancer (Flores-Holguín et al. 2021). For the AMES test, none of the compounds are positive. None of the compounds are inhibitors of hERG2-I. Compounds 2 and 4 are inhibitors of hERG II. MRDT (Maximum tolerated dose) is the maximum tolerated dose that predicts the values of the toxic dose threshold of chemicals in humans. The recommended value for MRDT is ≤ 0.477 log (mg/kg/day), which is considered low and high if > 0.477. Only Compound 6 shows a high (− 0.863) MRDT, and the remaining has a low. Many drugs cause liver injuries. Hence, it is a safety concern for drug development. Only compound 3 showed hepatotoxicity. Compounds 3, 4, and 5 are showing skin sensitization. Remaining, not showing any skin sensitization. T. pyriformis is a protozoan bacterium, and its toxicity is frequently used as a toxic endpoint. A value > − 0.5 log ug/L is considered toxic. All the selected compounds show toxicity to this.

Antibacterial studies

Methanol and aqueous extracts of stem and callus derived from stem and tuber extracts were screened for antibacterial activity against Bacillus subtilis, Escherichia coli, and Proteus vulgaris, and zones of inhibition were recorded after 24 h, as presented in Table 3 (Fig. 5a, b, c, d, e, f).

Table 3.

Growth of inhibition of various extracts of Kedrostis foetidissima against bacterial cultures

S. No Organism Methanol extract (20 μL) Aqueous extract (20 μL)
SC S T SC S T
1 Bacillus subtilis 18 17 12 13 8 6
2 Escherichia coli 19 16 6 12 10 5
3 Proteus vulgaris 18 16 10 14 11 8
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Values indicates zone of inhibition in mm

SC stem callus, S stem, T tuber

Fig. 5.

Fig. 5

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a Growth of inhibition with stem, stem callus and tuber extracts of Kedrostis foetidissima-Methanol extracts against Bacillus subtillis. b Growth of inhibition with stem, stem callus and tuber extracts of Kedrostis foetidissima-Aqueous extracts against Bacillus subtillis. c Growth of inhibition with stem, stem callus and tuber extracts of Kedrostis foetidissima-Methanol extracts against Escherichia coli. d Growth of inhibition with stem, stem callus and tuber extracts of Kedrostis foetidissima-Aqueous extracts against Escherichia coli. e Growth of inhibition with stem, stem callus and tuber extracts of Kedrostis foetidissima- Methanol extracts against Proteus vulgaris. f Growth of inhibition with stem, stem callus and tuber extracts of Kedrostis foetidissima-Aqueous extracts against Proteus vulgaris

Methanol and aqueous extracts of stem extracts showed the highest activity against Escherichia coli, with 16 mm and 10 mm zones of inhibition, respectively. In contrast to our results, ethanol extracts of stem and leaf showed less activity against Escherichia coli. This is because different solvent extracts have different chemical compounds. The highest zone of inhibition, about 17 mm, was achieved against Basillus subtilis in methanol extract. Whereas acetone and chloroform extracts showed less response to Basillus subtilis. 11 mm of zone of inhibition against Proteus vulgaris was observed in aqueous solvents.

The antibacterial activity of methanol extracts of stem callus against Escherichia coli is greater than the antibiotic activity of gentamicin and tetracycline (Raja et al. 2019). For Bacillus subtilis, the highest zone of inhibition was about 18 mm and 13 mm, respectively, for the ethanol and aqueous extracts recorded. Methanol and aqueous extracts of stem callus extracts showed the highest activity against Proteus vulgaris, with 18 mm and 14 mm zones of inhibition, respectively. Similarly, callus cultures showed a higher zone of inhibition against E. coli in Clitoria ternatea than root extracts (Malabadi et al. 2012). With our results, it is proven that the in vitro-derived calli tissue was more effective compared to the in vivo tissue in terms of antibacterial activity (Shariff et al. 2006).

Among all plant extracts studied, tuber extracts showed the least response against all the studied organisms. Highest activity against Bacillus subtilis and Proteus vulgaris with 12 mm and 10 mm zones of inhibition, respectively, in methanol extracts. This proves that aerial parts show the highest inhibition activity compared to underground parts against microbes. Similar results were achieved in Gentiana asclepiadea (Vladimir et al. 2011).

In our results, methanol extracts of stem callus, stem, and tuber extracts showed more inhibition of the growth of bacteria than aqueous extracts. Similar reports were achieved with extracts of Boerhaavia diffusa, Tinospora cardiofolia, and Eclipta alba (Girish and Satish 2008). In vitro-derived stem, callus proved more bacterial efficacy than in vivo plant material, i.e., stem and tuber.

In the present work, the six compounds of the Kedrostis foetidissima plant were tested for in silico ADMET profiling and drug-likeness properties using the Swiss ADME online web server and the pkCSM server. All the studied compounds are obeying Lipinski's rule of five except compounds 1 and 2, with two and three violations each. All the selected compounds from Kedrostis foetidissima have strong pharmacological activities. Supporting this, the selected plant methanol extracts of leaf, stem callus, and tuber have shown well in vitro antibacterial activity against Bacillus subtilis, Escherichia coli, and Proteus vulgaris.

Conclusion

Based on the physicochemical properties such as molecular weight and topological polar surface area (TPSA) whose upper limits are formulated by Lipinski’s rule of five and Veber’s filter. An orally active compound must pursue molecular weight under 500 g/mol, TPSA underneath 120 Å. The molecule 2 and 6 show more than 500 g/mol molecular weight and molecule 1,2 show more than 120 Å2 TPSA values. Compounds 3, 4, 5, and 6 obey Lipinski's rule of five except compound 1 and 2, with 2 and 3 violations each. Even though compound 1 and 2 can be used for drug development because they are biologically active natural products. The entire selected compounds have a good bioavailability score in a recommended range of 0 to 1. Compound 4 has high (0.85) and compounds 1 and 2 have low (0.17) oral bioavailability scores. Most of them show acceptable ADMET properties. Analysis of the Drug likeness and ADMET parameters for the selected compounds predicted good drug-like properties. Therefore, these compounds have agreeable pharmacological properties that can be developed as an oral drug candidate. In our results, among all the plant extracts studied, the methanol extract of stem callus showed the highest inhibition against all the selected organisms. This research also demonstrated the presence of medicinally significant bioactive components in the investigated plant, supporting their usage in traditional medicines for the treatment of various illnesses. These results suggest that they could be studied further for in vitro and in vivo studies for particular pharmacological activities and docking studies for specific proteins to develop as drug molecules.

Acknowledgements

The authors are thankful to Dr. G. Renuka, Assistant Professor of Chemistry, Department of Microbiology, Pingle Govt. College for Women (A), Hanumakonda, 506370, Telangana, India, for providing bacterial cultures.

Author contributions

Dr. Kommidi Saritha: Conceptualization, writing original draft, Investigation, Methodology, Writing. Dr. Muangala Alivelu: Software, Data curation, Formal analysis. Prof. Mustafa Mohammad: Review, Editing, Resources.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Conflict of interest

The authors declared that they have no known competing financial interests with respect to the research, authorship and/or publication of this article. The authors declare no competing interests.

Ethical approval

Not applicable.

Informed consent

Not applicable.

Footnotes

Publisher's Note

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