Molecular Properties, Bioactivity Scores, and Toxicity Predictions of the Phytoconstituents Present in Bauhinia Acuminata

: To develop the herbal drug with the least side effects, there are superior opportunities to discover the medicinal and other biological properties. Natural products serve as sources of beneficial chemical molecules. For this study, Bauhinia acuminata an important medicinal plant of the Indian subcontinent that belongs to the family Fabaceae was chosen. The plant is well known for its precautionary action in tuberculosis. It has been established to possess some pharmacological activities such as membranes Stabilizing activity1, antibacterial2, anti-nociceptive3, thrombolytic activity4, antioxidant5, anthelmintic6, anti-diarrheal7, Hepato-protective 8. Phytoconstituents present in Bauhinia acuminata obey Lipinski's rule (MiLog P <5) except Kaempferol-3-glucoside indicated their drug-likeness property. Rhoeagenine, 9, 12, 15-octadecatrienoic acid, and 9, 12-octadecadienoic acid are the phytoconstituents showing all types of binding with all types of receptors binding except Kinase inhibitor activity. Rhoeagenine, Alpha humulene, 9, 12, 15-octadecatrienoic acid, 9, 12-octadecadienoic acid, Alpha muurolol, Beta-sitosterol, Kaempferol-3-glucoside are the phytoconstituents that are free from any type of toxicity. The accurate prediction scores can be used as monographs by researchers and scientists for the development of potential Semisynthetic and synthetic drugs for multifarious usage.


Abstract:
To develop the herbal drug with the least side effects, there are superior opportunities to discover the medicinal and other biological properties. Natural products serve as sources of beneficial chemical molecules. For this study, Bauhinia acuminata an important medicinal plant of the Indian subcontinent that belongs to the family Fabaceae was chosen. The plant is well known for its precautionary action in tuberculosis. It has been established to possess some pharmacological activities such as membranes Stabilizing activity1, antibacterial2, anti-nociceptive3, thrombolytic activity4, antioxidant5, anthelmintic6, anti-diarrheal7, Hepato-protective 8. Phytoconstituents present in Bauhinia acuminata obey Lipinski's rule (MiLog P <5) except Kaempferol-3glucoside indicated their drug-likeness property. Rhoeagenine, 9, 12, 15-octadecatrienoic acid, and 9, 12octadecadienoic acid are the phytoconstituents showing all types of binding with all types of receptors binding except Kinase inhibitor activity. Rhoeagenine, Alpha humulene, 9, 12, 15-octadecatrienoic acid, 9, 12-octadecadienoic acid, Alpha muurolol, Beta-sitosterol, Kaempferol-3-glucoside are the phytoconstituents that are free from any type of toxicity. The accurate prediction scores can be used as monographs by researchers and scientists for the development of potential Semisynthetic and synthetic drugs for multifarious usage.

I.
Introduction: The prehistoric people have great consciousness of the tradition of medicinal plants as herbal medicines. In the world, more than 80% of the living in minor developed countries reveals on customary medicine and humans are dependent on herbs for their basic requirements such as foodstuffs, clothing, flavor, shelter, fragrance, and medicines (Divya and Mini, 2011& Manoj Kumar Mishra, 2016, Gurib-Fakim, 2006and Brijesh & Madhusudan, 2015. The Discovery of drugs in medicinal plants affords better and vital leads, besides diverse pharmacological activities such as cytotoxic, anti-diarrheal, antimicrobial, antiinflammatory, antioxidant, anthelmintic, anti-nociceptive, hemolytic activity. The plant is well known for its precautionary action in tuberculosis. As per the recommendations of Ayurveda Bauhinia acuminata is the one of important medicinal plants for the treatment of disorders. (Yi F et al, 2016) 9 .

Molinspiration i)
Lipinski's rule Lipinski's rule of five also known as Pfizer's rule of five or simply the Rule of five (RO5) is a rule of thumb to evaluate drug-likeness or determine if a chemical compound with a certain pharmacological or biological activity has properties that would make it a likely orally active drug in humans. The rule was formulated by Christopher A. Lipinski in 1997. The rule describes molecular properties important for a drug's pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion ("ADME") Components of Lipinski's rule: ii) Lipinski's rule states  A molecular mass of fewer than 500 daltons.  An octanal-water partition coefficient log P not greater than 5.  Not more than 10 hydrogen bond acceptors (nitrogen or oxygen atoms).  Not more than 5 hydrogen bond donors (nitrogen or oxygen atoms with one or more hydrogen atoms).  No more than one violation.

iii)
Drug likeness score Molinspiration is web-based software which can be used to obtain parameters such as MiLog P, druglikeness scores, TPSA. MiLog P is calculated by the methodology developed by Molinspiration which is a sum of fragment-based contributions and correction factors. Good permeability across the cell membrane can be checked with MiLog P value. Log P or Partition coefficient is an important parameter used to measure molecular hydrophobicity in rational drug design. The hydrophilic/lipophilic nature of drug molecules affects drug absorption, bioavailability, drug-receptor interactions, as well as their toxicity. Based on a sum of fragment contributions of O and N-centered polar fragments Molecular Polar Surface Area TPSA is calculated. Total polar surface area (TPSA) is closely related to the hydrogen bonding potential of a molecule and is a very good predictor of drug transport properties such as intestinal absorption, bioavailability, blood-brain barrier penetration, etc. Based on group contributors, the calculation of volume were developed at Molinspiration The number of rotatable bonds measures molecular flexibility. It is a very good descriptor of the absorption and bioavailability of drugs. Molecular properties and structure features with respect to known drugs can be checked through drug-likeliness data of the molecule. MiLog P (partition coefficient), molecular weight, number of heavy atoms, number of hydrogen donors, number of hydrogen acceptors and number of violations, number of rotatable bonds, and volume 11 are the parameters considered for calculating the drug-likeness scores.

iv)
Bioactivity score Bioactivity of the drug can be checked by calculating the activity score of GPCR ligand, ion channel modulator, nuclear receptor legend, a kinase inhibitor, protease inhibitor, enzyme inhibitor. Calculated drug-likeness score of each compound and compared with the specific activity of each compound, and the results were compared with standard drug. All the parameters were checked with the help of the software Molinspiration drug-likeness score online (www.molinspiration.com). The probability for the organic molecules is if the bioactivity score is (>0), then it is active, if (-5.  Table 1 were selected for Insilco prediction and the smile notations of used to generate the data.

ii)
Methods: Molinspiration Software: Structures of 13 phytochemical compounds selected for our work as given in Table 1 (reported in the literature resources) were drawn using online molinspiration for the calculation of molecular properties like MiLog P, Total polar surface area (TPSA), number of hydrogen bond donors and acceptors, molecular weight, number of atoms, number of rotatable bonds, etc., and bioactivity scores like GPCR ligands, kinase inhibitors, ion channel modulators, enzymes, and nuclear receptors. The molecular properties and bioactivity scores predicted by molinspiration were given in Tables-2 and 3.
Osiris software: (https://www.Osiris.com) This software predicts the toxicity risk assessment and calculates on-the-fly various drug-relevant properties like cLogP, solubility, Molecular Weight, Toxicity Risk Assessment, Overall Drug-Score, etc. When the structure is valid Prediction results are valued and colorcoded like properties with a high risk of undesirable effect shown in red whereas green color indicates drugconform behavior.      Table 1: General properties and structures of the phytoconstituents present in Bauhinia acuminata Table 2    Rhoeagenine, Alpha humulene, 9, 12, 15-octadecatrienoic acid, 9,12-octadecadienoic acid, Alpha muurolol, Beta-sitosterol, Kaempferol-3-glucoside are the phytoconstituents that are free from any type of toxicity.

Conclusion
In the present study, we used Molinspiration, Osiris online software tool which is available free for the users to evaluate the molecular properties, bioactivity scores, toxicity predictions of the phytoconstituents present in Bauhinia acuminata. The phytoconstituents of the plants were enlisted through the software includes Quercetin, Neophytadiene, Rhoeagenine, Alpha humulene, Butanedioic acid diethyl ester, 9,12,15octadecatrienoic acid, Beta-ionone, 9,12-octadecadienoic acid, Alpha muurolol, Bauhinione, Kaempferol-3-glucoside. Accordingly, the respective software data for the phytoconstituents are computed and depicted in respective tables. Further, these values can be used as monographs by researchers and scientists for the development of potential Semisynthetic and synthetic drugs for multifarious usage.