The success or failure of a potential drug depends on its absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics, and these features are usually rate-limiting in the drug development process. Hence, it is essential to know about the predicted ADMET properties of the most promising leads to avoid the risk of late-stage attrition. This project focuses on in silico screening of ADMET properties of phytochemicals found in Dakshina Kannada's medicinal plants, which include Tinospora cordifolia, Azadirachta indica, Ocimum sanctum, and Plectranthus amboinicus, mainly known for their antimicrobial properties.The physicochemical properties, bioactivity scores, ADMET, and molecular interactions of the selected phytoconstituents were determined by QikProp, Molinspiration, ADMETlab 2.0, ProTox-II, and GLIDE. In addition, molecular docking checked for their binding interactions with target proteins 1JIJ and 4 HOE of Staphylococcus aureus and Candida albicans, respectively, as they were well known for their antimicrobial properties. In this studies, rosmarinic acid was well interacted phytochemical with both target proteins and has highest docking score.The physicochemical properties showed that all compounds fell under the recommended molecular weight, volume, and polar surface area range. Xanosporic acid violated two rules of Lipinski's Rule of Five, indicating that it may have problems with oral bioavailability. The ADME properties for most of the phytocompounds were within the recommended ranges; hence, they are promising candidates for drug development. Most phytoconstituents showed good bioactivity scores, indicating they have good druglikeness properties. On the analysis of the toxicity, most of the phytoconstituents were found to be noncarcinogenic and nonmutagenic. Therefore, this data can further be utilized as primary tools for determining the biological actions of these plants.Xanosporic acid was found to violate two out of three rules of Lipinski. Similarly, ursolic acid and oleanolic acid also showed a few undesirable properties. All other compounds otherwise showed desirable properties and hence are promising candidates for drug development. This data can be further utilized as primary tool for determining the biological actions of the plants.

Nitrogen heterocyclic compounds such as pyrazolines have been found to possess a broad spectrum of biological activities such as anticancer, antitubercular, anti-inflammatory, analgesic, and antidepressant activities. Pyrazoline derivatives IV, V (a-e) have been synthesized from the intermediate chalcones III (a-h) by cyclizing with phenyl hydrazine and hydrazine hydrate. The structures of these compounds were confirmed by IR, NMR, and mass spectroscopy. Biological studies of the synthesized compounds showed promising antitumor, analgesic, and anti-inflammatory activities. The compounds were tested for their in vitro antitumor activity against EAC tumor cell lines. Compounds IVa and IVb showed the highest cytotoxicity of 80% at a 200 μg mL concentration. Among the tested compounds, IVa and Vd seem to be more effective analgesic agents. Compounds IVc, IVd, and Ve are found to be the most effective anti-inflammatory agents. Thus the results show that synthesized compounds possess antitumor, analgesic, and anti-inflammatory activity. It was observed that the test compounds with electron withdrawing groups (halogens) on the aromatic ring favors antitumor, analgesic, and anti-inflammatory activity. Key words: Analgesic,anti-inflammatory activity,antitumor,chalcones,pyrazolines.

Various targets, such as estrogen receptor (ER), mammalian target ofrapamycin(mTOR), epidermal growth factor receptor (EGFR), androgen receptor (AR) andpoly adenosine diphosphate-ribose polymerase (PARP), are focused on the treatment of breast cancer. In this study, in silico tools such as pharmacophore modeling, 3D QSAR study, molecular docking, binding free energy determination and molecular dynamics were executed on a series of pyrazolopyrimidines derivatives. The pharmacophore modeling of forty-one anticancer derivatives was generated, and atom-based 3D QSAR was applied. Molecular docking, dynamics, binding energy and high-throughput virtual screening (HTVS) were conducted by the software Schrodinger. The best five featured pharmacophore hypotheses AHRRR_1 with a maximum survival score of 5.533 was subjected to rigorous scoring function analysis and 3D QSAR studies. Docking studies and binding free energy were carried out on 41 inhibitors for their anti-breast cancer activity against human estrogen, progesterone receptor, EGFR kinase and mammalian target of rapamycin mTOR. Molecular dynamics simulation of the docked complex-34/4WKQ validated the stability of this complex. HTVS was performed to determine the virtual hits with the best-fitted model AHRRR_1. New EGFR kinase inhibitors were designed based on the active compound templates. Molecular docking was carried out on virtual hits, and newly designed compounds and dynamics studies revealed that the binding modes obtained after MD simulation were more or less similar to that acquired post docking mode. Promiscuity assessments demonstrated that designed compounds would be specific rather than a promiscuous one. Based on these findings, we have designed four novel compounds as anti-breast inhibitors, with potent binding affinity and desirable ADME properties.

Cyclooxygenase (COX), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins. Prostaglandins promote inflammation. Blockage of COX enzymes reduces prostaglandins and thus their effects are reduced. The present study focuses on In silico ADMET, molecular docking studies and binding energy calculations of ten pyrimidine derivatives as cox-1 and cox-2 inhibitors. Molecular docking studies were conducted on two target enzymes. Energy minimisation of the ligands was carried out using ligprep. They were docked to the active site of the proteins using the extra precision mode of glide module. The docked poses were ranked according to their docking score and binding energy with the enzymes. Compound PY4 showed better docking score with cox-1 (−6.081 kcal/mol) and compound PY5 showed good docking score with cox-2 (−8.602 kcal/mol). All compounds were found to have good docking and binding affinity scores when compared to the standards. Thus it reveals that the synthesised compounds act as anti-inflammatory agents by inhibiting cox-1 and cox-2 enzymes.

The neuroprotective actions of flavonoids and alkaloids have been reported in many cognitive disorders. The study was focused on twenty-four phytoconstituents (alkaloids and flavonoids) to screen their activity against neurodegenerative diseases. The molecular interactions were analyzed between the phytoconstituents and the acetylcholinesterase and monoamine oxidase-B enzymes by computational studies such as molecular docking, binding free energy determination, molecular dynamics, pharmacophore modeling, and ADMET. The well-interacted compounds were piperine and rutin, which has high inhibitory potential than the enzymes' co-crystals. Molecular dynamics confirmed the stability of piperine-2V60 and rutin-6O4W complexes, and pharmacophore modeling studies confirmed the hydrogen bonding interactions. Physicochemical and ADMET properties were carried out, highlighting the druglikeness and oral bioavailability of the compounds. PASS online tool predicted the phytoconstituents biological spectrum against the enzyme involved in neurodegenerative diseases. Further, these compounds should be pharmacologically explored to develop as good leads for treating neurodegenerative diseases.