Reviewing the Synthesis and Clinical Application of FDA-Approved Anticancer Medications.

Cancer is a disease that affects people of all ages, socioeconomic backgrounds, genders, and demographics. It places a significant burden not just on those who are diagnosed but also on their families and communities. Targeted therapeutic medications have surpassed more conventional forms of chemotherapy in terms of both their effectiveness and safety, which leads to their rapid ascent to the forefront of cancer treatment. A growing number of small molecules have been created for the treatment of cancer, and several of these drugs have been approved to be sold in the market by the Food and Drug Administration of the United States. Small molecule targeted anticancer therapies have made significant progress in recent years, yet they continue to struggle with a number of obstacles, including a low response rate and drug resistance. We have carried out an exhaustive study on approved small-molecule targeted anticancer medications, as well as important drug candidates. This review describes the significance of approved anticancer drugs from 2021 to 2024, clinically active anticancer drugs, and the methods used for their synthesis.

Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies.

INTRODUCTION: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential. METHOD: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 µM. The derivative 5h, with an IC50 of 13.60 ± 2.51 µM, emerged as the most potent inhibitor. RESULTS: Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of -6.30 Kcal/- mol, consistent with experimental results. CONCLUSION: All findings underscored the potential of synthesized derivatives for drug development.

Molecular Hybrid Design, Synthesis, In Vitro Cytotoxicity, In Silico ADME and Molecular Docking Studies of New Benzoate Ester-Linked Arylsulfonyl Hydrazones.

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 µM for the A549 cell line and 27.70-170.30 µM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 µM against A549 cell line and IC50 = 27.70 µM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 µM against A549 cell line and IC50 = 18.01 µM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

Analysis of Chemical Composition, Antioxidant Activity, and Toxicity of Essential Oil from Virola sebifera Aubl (Myristicaceae).

Volatile oils or essential oils (EOs) were extracted from three V. sebifera samples (labeled as A, B, and C) in September 2018 and February 2019; the extraction process involved hydrodistillation of the leaves. The chemical compositions of the EOs were analyzed using gas chromatography-mass spectrometry (GC/MS). The volatile components were identified by comparing their retention indices and mass spectra with standard substances documented in the literature (ADAMS). The antioxidant activity of the EOs was evaluated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), while their toxicity was assessed using Artemia salina Leach. Molecular docking was utilized to examine the interaction between the major constituents of V. sebifera EO and acetylcholinesterase (AChE), a molecular target linked to toxicity in A. salina models. The EO obtained from specimen A, collected in September 2018, was characterized by being primarily composed of (E,E)-α-farnesene (47.57%), (E)-caryophyllene (12.26%), and α-pinene (6.93%). Conversely, the EO from specimen A, collected in February 2019, was predominantly composed of (E,E)-α-farnesene (42.82%), (E)-caryophyllene (16.02%), and bicyclogermacrene (8.85%), the EO from specimen B, collected in September 2018, primarily contained (E,E)-α-farnesene (47.65%), (E)-caryophyllene (19.67%), and α-pinene (11.95%), and the EO from the leaves collected in February 2019 was characterized by (E,E)-α-farnesene (23.57%), (E)-caryophyllene (19.34%), and germacrene D (7.33%). The EO from the leaves collected in September 2018 contained (E,E)-α-farnesene (26.65%), (E)-caryophyllene (15.7%), and germacrene D (7.72%), while the EO from the leaves collected in February 2019 was primarily characterized by (E,E)-α-farnesene (37.43%), (E)-caryophyllene (21.4%), and α-pinene (16.91%). Among these EOs, sample B collected in February 2019 demonstrated the highest potential for inhibiting free radicals, with an inhibition rate of 34.74%. Conversely, the EOs from specimen A exhibited the highest toxic potentials, with an lethal concentration 50 (LC50) value of 57.62 ± 1.53 µg/mL, while specimen B had an LC50 value of 74.72 ± 2.86 µg/mL. Molecular docking results suggested that hydrophobic interactions significantly contributed to the binding of the major compounds in the EO from sample B to the binding pocket of AChE.

Design, synthesis, and in vitro and in silico studies of morpholine derived thiazoles as bovine carbonic anhydrase-II inhibitors.

Carbonic anhydrase CA-II enzyme is essential for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance due to its vital function within cellular processes. Herein, we screened 25 newly synthesized thiazole derivatives and assessed their inhibitory potential against the zinc-containing carbonic anhydrase CA-II enzyme. Intriguingly, derivatives of thiazole exhibited varying degrees of inhibitory action against CA-II. The distinctive attribute of these compounds is that they can attach to the CA-II binding site and block its action. Morpholine based thiazoles can be strategically modified to improve bovine CA-II inhibitor binding affinity, selectivity, and pharmacokinetics. Thiazole and morpholine moieties can boost inhibitory efficacy and selectivity over other calcium-binding proteins by interacting with target bovine CA-II binding sites. The derivatives 23-26 exhibited greater affinity when compared to the standard acetazolamide. Furthermore, kinetic study of the most potent compound 24 was performed, which exhibited concentration dependent inhibition with a K i value of 9.64 ± 0.007 µM. Molecular docking, MD simulation and QSAR analysis was also carried out to elucidate the interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, pharmacokinetic assessments showed that most of the compounds possess attributes conducive to potential drug development.

An Ethnopharmacological Survey on Medicinally Important Plants of Genus Salvia.

Lamiaceae (Labiatae) is a medicinally significant plant family featuring key species like Salvia aegyptiaca, S. cabulica, S. coccinea, S. glutinosa, S. officinalis, S. haematodes, S. hians, S. lanata, S. macrosiphon, S. moorcroftiana, S. spinosa, S. sclarea, and S. plebeia. These species exhibit diverse pharmacological activities attributed to essential oils and phytochemi-cals, including antioxidant, antiasthmatic, antitumor, anti-inflammatory, analgesic, etc. This re-view covers extensive phytomedicinal aspects of some important plants of the genus Salvia.

Development of curcumin integrated smart pH indicator, antibacterial, and antioxidant waste derived Artocarpus lakoocha starch-based packaging film.

Monitoring of food freshness is considered one of the crucial challenges for both customers/consumers and the food industries. In this study, we developed a curcumin-based starch film (F1) for pH-sensitive intelligent food packaging application. The starch was obtained from waste seeds of Artocarpus lakoocha (NS-MJF). The native starch underwent various physical and chemical modifications to yield modified starches (S1 [Autoclave heat treated], S2 [osmotic-pressure treated], S3 [citric acid treated]). The native starch was then used further for the formation of curcumin (2.5 % w/w)-based film (F1). We had analyzed these starches for solubility, colour analysis, biodegradability, oil absorption capacity, and moisture content, etc. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed favourable microstructures. The addition of curcumin to the starch enhanced the contact angle and elongation at the break of the resulting films. Antioxidant and antimicrobial assays, along with real-time freshness monitoring of chicken fillets, were also conducted. Thus, our findings may contribute to the optimization of pH-responsive biopolymer-based films for intelligent poultry packaging, promising advancements in food preservation and safety.

Synthesis, biological evaluation, and molecular modelling of substituted thiazolyl thiourea derivatives: A new class of prolyl oligopeptidase inhibitors.

Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors. The current study seeks to contribute to the identification of efficacious POP inhibitors through the design, synthesis, and comprehensive evaluation (both in vitro and in silico) of thiazolyl thiourea derivatives (5a-r). In vitro experimentation exhibited that the compounds displayed significant higher potency as POP inhibitors. Compound 5e demonstrated an IC50 value of 16.47 ± 0.54 µM, representing a remarkable potency. A meticulous examination of the structure-activity relationship indicated that halogen and methoxy substituents were the most efficacious. In silico investigations delved into induced fit docking, pharmacokinetics, and molecular dynamics simulations to elucidate the intricate interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, our pharmacokinetic assessments confirmed that the majority of the synthesized compounds possess attributes conducive to potential drug development.

Synthesis and antiproliferative evaluation of novel 3,5,8-trisubstituted coumarins against breast cancer.

Aim: This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. Results: The synthesized compounds, particularly compound 5, exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 5 altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIß expression. Molecular modeling indicated compound 5's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. Conclusion: These findings highlight compound 5 as a multifaceted antitumor agent for breast cancer.

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From lab to nature: Recent advancements in the journey of gastroprotective agents from medicinal chemistry to phytotherapy.

Peptic ulcer, affecting 10 % of the global population, results from imbalances in gastric juice pH and diminished mucosal defences. Key underlying factors are non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection, undermining mucosal resistance. Traditional treatments like proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists exhibit drawbacks such as adverse effects, relapses, and drug interactions. This review extensively explores the ethnomedicinal, synthetic and pharmacological facets of various potential peptic ulcer treatments. Rigorous methodologies involving electronic databases, and chemical structure verification via 'PubChem' and 'SciFinder' enhance the review's credibility. The provided information, spanning medicinal insights to intricate pharmacological mechanisms, establishes a robust groundwork for future research and the development of plant-derived or synthetic molecules for peptic ulcers, offering a promising alternative to conventional therapies.

Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein.

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 µM, ~2183-fold higher than acarbose having an IC50 of 873.34 ± 1.67 µM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.

Chemical Composition of Piper nigrum L. Cultivar Guajarina Essential Oils and Their Biological Activity.

The essential oils and aroma derived from the leaves (L), stems (St), and spikes (s) of Piper nigrum L. cv. Guajarina were extracted; the essential oils were extracted using hydrodistillation (HD), and steam distillation (SD), and the aroma was obtained by simultaneous distillation and extraction (SDE). Chemical constituents were identified and quantified using GC/MS and GC-FID. Preliminary biological activity was assessed by determining the toxicity against Artemia salina Leach larvae, calculating mortality rates, and determining lethal concentration values (LC50). The predominant compounds in essential oil samples included α-pinene (0-5.6%), ß-pinene (0-22.7%), limonene (0-19.3%), 35 linalool (0-5.3%), δ-elemene (0-10.1%), ß-caryophyllene (0.5-21.9%), γ-elemene (7.5-33.9%), and curzerene (6.9-31.7%). Multivariate analysis, employing principal component analysis (PCA) and hierarchical cluster analysis (HCA), revealed three groups among the identified classes and two groups among individual compounds. The highest antioxidant activity was found for essential oils derived from the leaves (167.9 41 mg TE mL-1). Larvicidal potential against A. salina was observed in essential oils obtained from the leaves (LC50 6.40 µg mL-1) and spikes (LC50 6.44 µg mL-1). The in silico studies demonstrated that the main compounds can interact with acetylcholinesterase, thus showing the potential molecular interaction responsible for the toxicity of the essential oil in A. salina.

Carbonylbis(hydrazine-1-carbothioamide) derivatives as a new class of α-glucosidase inhibitors and their mechanistic insights via molecular docking and dynamic simulations.

In the past, efforts have been made to find a cure for diabetes, mainly evaluating new classes of compounds to explore their potency. In this study, we present the synthesis and evaluation of carbonylbis(hydrazine-1-carbothioamide) derivatives as potential α-glucosidase inhibitors, employing both in vivo and in silico investigations. The in vitro experiments revealed that all tested compounds were significantly potent for α-glucosidase inhibition, with the lead compound 3a displaying approximately 80 times higher activity than acarbose. To delve deeper, in silico induced fit docking, pharmacokinetics, and molecular dynamics studies were conducted. Significantly, compound 3a exhibited a docking score of -7.87 kcal/mol, surpassing acarbose, which had a docking score of -6.59 kcal/mol. The in silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development. Molecular dynamics analysis demonstrated that, when the ligand 3a was coupled with the target 3TOP, Cα-RMSD backbone RMSD values below 2.4 Å and "Lig_fit_Prot" values below 2.7 Å were observed. QSAR analysis demonstrates that the "fOC8A" descriptor positively correlates with α-glucosidase inhibition activity, while "lipoplus_AbSA" positively contributes and "notringC_notringO_8B" negatively contributes to this activity.

Novel 2-substituted-quinoxaline analogs with potential antiproliferative activity against breast cancer: insights into cell cycle arrest, topoisomerase II, and EGFR activity.

Breast cancer is a global health concern, with increasing disease burden and disparities in access to healthcare. Late diagnosis and limited treatment options in underserved areas contribute to poor outcomes. In response to this challenge, we developed a novel family of 2-substituted-quinoxaline analogues, combining coumarin and quinoxaline scaffolds known for their anticancer properties. Through a versatile synthetic approach, we designed, synthesized, and characterized a set of 2-substituted quinoxaline derivatives. The antiproliferative activity of the synthesized compounds was assessed toward the MCF-7 breast cancer cells. Our investigations showed that the synthesized compounds exhibit considerable antiproliferative activity toward MCF-7 cells. Notably, compound 3b, among examined compounds, displayed a superior inhibitory effect (IC50 = 1.85 ± 0.11 µM) toward the growth of MCF-7 cells compared to the conventional anticancer drug staurosporine (IC50 = 6.77 ± 0.41 µM) and showed minimal impact on normal cells (MCF-10A cell lines, IC50 = 33.7 ± 2.04 µM). Mechanistic studies revealed that compound 3b induced cell cycle arrest at the G1 transition and triggered apoptosis in MCF-7 cells, as evidenced by increasing the percentage of cells arrested in the G2/M and pre-G1 phases utilizing flow cytometric analysis and Annexin V-FITC/PI analysis. Moreover, compound 3b was found to substantially suppress topoisomerase enzyme activity in MCF-7 cells. Molecular modeling studies further supported the potential of compound 3b as a therapeutic candidate by demonstrating significant binding affinity to the active sites of both topoisomerase II and EGFR proteins. Taken together, the presented 2-substituted-quinoxaline analogues, especially compound 3b, show promise as potential candidates for the development of effective anti-breast cancer drugs.

Chemical Composition, Preliminary Toxicity, and Antioxidant Potential of Piper marginatum Sensu Lato Essential Oils and Molecular Modeling Study.

The essential oils (OEs) of the leaves, stems, and spikes of P. marginatum were obtained by hydrodistillation, steam distillation, and simultaneous extraction. The chemical constituents were identified and quantified by GC/MS and GC-FID. The preliminary biological activity was determined by assessing the toxicity of the samples to Artemia salina Leach larvae and calculating the mortality rate and lethal concentration (LC50). The antioxidant activity of the EOs was determined by the DPPH radical scavenging method. Molecular modeling was performed using molecular docking and molecular dynamics, with acetylcholinesterase being the molecular target. The OES yields ranged from 1.49% to 1.83%. The EOs and aromatic constituents of P. marginatum are characterized by the high contents of (E)-isoosmorhizole (19.4-32.9%), 2-methoxy-4,5-methylenedioxypropiophenone (9.0-19.9%), isoosmorhizole (1.6-24.5%), and 2-methoxy-4,5-methylenedioxypropiophenone isomer (1.6-14.3%). The antioxidant potential was significant in the OE of the leaves and stems of P. marginatum extracted by SD in November (84.9 ± 4.0 mg TE·mL-1) and the OEs of the leaves extracted by HD in March (126.8 ± 12.3 mg TE·mL-1). Regarding the preliminary toxicity, the OEs of Pm-SD-L-St-Nov and Pm-HD-L-St-Nov had mortality higher than 80% in concentrations of 25 µg·mL-1. This in silico study on essential oils elucidated the potential mechanism of interaction of the main compounds, which may serve as a basis for advances in this line of research.

Synthesis, biological evaluation and molecular modelling of 3-Formyl-6-isopropylchromone derived thiosemicarbazones as α-glucosidase inhibitors.

Type-2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders in the world and over the past three decades its incidence has increased drastically. α-Glucosidase inhibitors are used to control the hyperglycemic affect of T2DM. Herein, we report the synthesis, α-glucosidase inhibition, structure activity relationship, pharmacokinetics and docking analysis of various novel chromone based thiosemicarbazones 3(a-r). The derivatives displayed potent activity against α-glucosidase with IC50 in range of 0.11 ± 0.01-79.37 ± 0.71 µM. Among all the synthesized compounds, 3a (IC50 = 0.17 ± 0.026 µM), 3 g (IC50 = 0.11 ± 0.01 µM), 3n (IC50 = 0.55 ± 0.02 µM), and 3p (IC50 = 0.43 ± 0.025 µM) displayed higher inhibitory activity as compared to the standard, acarbose. Moreover, we have developed a statistically significant 2D-QSAR model (R2tr:0.9693; F: 50.4647 and Q2LOO:0.9190), which can be used in future to further design potent thiosemicarbazones as inhibitors of α-glucosidase.

Variation in the Chemical Composition of Endemic Specimens of Hedychium coronarium J. Koenig from the Amazon and In Silico Investigation of the ADME/Tox Properties of the Major Compounds.

Four species of the genus Hedychium can be found in Brazil. Hedychium coronarium is a species endemic to India and Brazil. In this paper, we collected six specimens of H. coronarium for evaluation of their volatile chemical profiles. For this, the essential oils of these specimens were extracted using hydrodistillation from plant samples collected in the state of Pará, Brazil, belonging to the Amazon region in the north of the country. Substance compounds were identified with GC/MS. The most abundant constituent identified in the rhizome and root oils was 1,8-cineole (rhizome: 35.0-66.1%; root: 19.6-20.8%). Leaf blade oil was rich in ß-pinene (31.6%) and (E)-caryophyllene (31.6%). The results from this paper allow for greater knowledge about the volatile chemical profile of H. coronarium specimens, in addition to disseminating knowledge about the volatile compounds present in plant species in the Amazon region.

The anti-SARS-CoV-2 activity of novel 9, 10-dihydrophenanthrene derivatives: an insight into molecular docking, ADMET analysis, and molecular dynamics simulation.

Originating in Wuhan, the COVID-19 pandemic wave has had a profound impact on the global healthcare system. In this study, we used a 2D QSAR technique, ADMET analysis, molecular docking, and dynamic simulations to sort and evaluate the performance of thirty-nine bioactive analogues of 9,10-dihydrophenanthrene. The primary goal of the study is to use computational approaches to create a greater variety of structural references for the creation of more potent SARS-CoV-2 3Clpro inhibitors. This strategy is to speed up the process of finding active chemicals. Molecular descriptors were calculated using 'PaDEL' and 'ChemDes' software, and then redundant and non-significant descriptors were eliminated by a module in 'QSARINS ver. 2.2.2'. Subsequently, two statistically robust QSAR models were developed by applying multiple linear regression (MLR) methods. The correlation coefficients obtained by the two models are 0.89 and 0.82, respectively. These models were then subjected to internal and external validation tests, Y-randomization, and applicability domain analysis. The best model developed is applied to designate new molecules with good inhibitory activity values against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). We also examined various pharmacokinetic properties using ADMET analysis. Then, through molecular docking simulations, we used the crystal structure of the main protease of SARS-CoV-2 (3CLpro/Mpro) in a complex with the covalent inhibitor "Narlaprevir" (PDB ID: 7JYC). We also supported our molecular docking predictions with an extended molecular dynamics simulation of a docked ligand-protein complex. We hope that the results obtained in this study can be used as good anti-SARS-CoV-2 inhibitors.