Mayra Antunez-Mojica
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Mayra Antunez-Mojica has a total of 57 co-authors. Here are the top co-authors by number of shared publications:
- Laura Alvarez
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Cuernavaca CP 62209, Morelos, Mexico
12 shared publications - Araceli Guerrero-Alonso
Chemical Research Center-IICBA, Autonomous University of the State of Morelos, Av. Universidad 1001, Chamilpa, Cuernavaca 62209, Morelos, Mexico
7 shared publications - Leticia González-Maya
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
5 shared publications - Silvia Marquina-Bahena
Chemical Research Center-IICBA, Autonomous University of the State of Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, Mexico
5 shared publications - Alberto Marbán-González
Universidad Nacional Autónoma de México
2 shared publications - Alfonso Miranda‐Molina
LANEM—Centro de Investigaciones Químicas—IICBA, Universidad Autónoma del Estado de Morelos, Cuernavaca CP 62210, Morelos, Mexico
2 shared publications
Latest Publications
- Open Access
Chemical Characterization, Antioxidant Activity, Lactic Acid Bacteria Growth-Supporting Effect, and Polysaccharide-Based Formulations of Huitlacoche (Ustilago maydis) Extracts
Huitlacoche (Ustilago maydis) is an edible mushroom of interest as a source of bioactive compounds. This study characterized raw (RwH) and dry-cooked (DckH) huitlacoche extracts, evaluated their antioxidant activity and effects on lactic acid bacterial growth, and examined polysaccharide-based formulations prepared with these extracts. GC–MS analysis of the hexane fractions tentatively identified fatty acid ethyl esters, particularly ethyl linoleate, ethyl oleate, and ethyl palmitate, as major constituents based on relative peak areas, with more compound assignments obtained for RwH than for DckH. HPLC retention times and UV spectra matched those of authentic standards for 4-hydroxybenzoic, vanillic, p-coumaric, and ferulic acids, supporting their tentative identification. NMR analysis of isolated compounds confirmed the presence of 4-hydroxybenzoic acid and 6-methoxy-2-benzoxazolinone. RwH exhibited higher total phenolic content and greater radical-scavenging activity in the ABTS and DPPH assays. Both extracts supported lactic acid bacterial growth at 1 mg/mL. Chitosan- and alginate-based formulations exhibited distinct morphological features, while DLS measurements of the chitosan-based formulations revealed heterogeneous hydrodynamic size distributions. These findings highlight differences between raw and dry-cooked huitlacoche extracts and provide an initial characterization of polysaccharide-based formulations, laying the groundwork for further evaluation of extract retention, stability, and release.
Open AccessChemical Characterization, Antioxidant Activity, Lactic Acid Bacteria Growth-Supporting Effect, and Polysaccharide-Based Formulations of Huitlacoche (Ustilago maydis) Extracts
Huitlacoche (Ustilago maydis) is an edible mushroom of interest as a source of bioactive compounds. This study characterized raw (RwH) and dry-cooked (DckH) huitlacoche extracts, evaluated their antioxidant activity and effects on lactic acid bacterial growth, and examined polysaccharide-based formulations prepared with these extracts. GC–MS analysis of the hexane fractions tentatively identified fatty acid ethyl esters, particularly ethyl linoleate, ethyl oleate, and ethyl palmitate, as major constituents based on relative peak areas, with more compound assignments obtained for RwH than for DckH. HPLC retention times and UV spectra matched those of authentic standards for 4-hydroxybenzoic, vanillic, p-coumaric, and ferulic acids, supporting their tentative identification. NMR analysis of isolated compounds confirmed the presence of 4-hydroxybenzoic acid and 6-methoxy-2-benzoxazolinone. RwH exhibited higher total phenolic content and greater radical-scavenging activity in the ABTS and DPPH assays. Both extracts supported lactic acid bacterial growth at 1 mg/mL. Chitosan- and alginate-based formulations exhibited distinct morphological features, while DLS measurements of the chitosan-based formulations revealed heterogeneous hydrodynamic size distributions. These findings highlight differences between raw and dry-cooked huitlacoche extracts and provide an initial characterization of polysaccharide-based formulations, laying the groundwork for further evaluation of extract retention, stability, and release.
- Open Access
- 19 October 2026
- Published by Frontiers Media SA in Frontiers in Plant Science
- Vol. 17, 1869172
Lignans: current trends in production through plant tissue culture, biological activities, and formulation methods
Lignans constitute an important class of plant secondary metabolites, widely distributed throughout the plant kingdom and biosynthesized via the oxidative coupling of phenylpropane units. These phenolic compounds have become key components of translational medicine and the nutraceutical industry, thanks to their wide range of biological activities. These activities include antitumor, antioxidant, anti-inflammatory, antiviral, neuroprotective, cardioprotective, and hormone-modulating effects, making them strategic candidates for treating chronic degenerative diseases with high global prevalence. However, harnessing their therapeutic potential presents significant challenges, as their taxonomic distribution is limited and their concentrations are concentrated in a few plant families, thereby hindering their commercial availability. Furthermore, the stereochemical complexity of their structures, characterized by multiple chiral centers, imposes significant barriers to total chemical synthesis and reduces the economic viability of synthetic routes. This gap between growing demand and limited natural supply underscores the urgent need to explore new plant species that produce lignans. In this context, this review critically examines the main sources of lignans, including direct extraction from plant biomass, chemical synthesis, and biotechnological production through callus cultures, cell suspensions, and hairy root cultures. The bioactivities and molecular mechanisms of lignans and neolignans obtained by biotechnological methods are further explored, including analyses of species distribution and molecular targets. Finally, the review discusses the advantages and limitations of different production platforms, challenges associated with industrial-scale production, and future perspectives for the sustainable and scalable development of lignan-based products.
- 19 October 2026
- Published by Frontiers Media SA in Frontiers in Plant Science
- Vol. 17, 1869172
Open AccessLignans: current trends in production through plant tissue culture, biological activities, and formulation methods
Lignans constitute an important class of plant secondary metabolites, widely distributed throughout the plant kingdom and biosynthesized via the oxidative coupling of phenylpropane units. These phenolic compounds have become key components of translational medicine and the nutraceutical industry, thanks to their wide range of biological activities. These activities include antitumor, antioxidant, anti-inflammatory, antiviral, neuroprotective, cardioprotective, and hormone-modulating effects, making them strategic candidates for treating chronic degenerative diseases with high global prevalence. However, harnessing their therapeutic potential presents significant challenges, as their taxonomic distribution is limited and their concentrations are concentrated in a few plant families, thereby hindering their commercial availability. Furthermore, the stereochemical complexity of their structures, characterized by multiple chiral centers, imposes significant barriers to total chemical synthesis and reduces the economic viability of synthetic routes. This gap between growing demand and limited natural supply underscores the urgent need to explore new plant species that produce lignans. In this context, this review critically examines the main sources of lignans, including direct extraction from plant biomass, chemical synthesis, and biotechnological production through callus cultures, cell suspensions, and hairy root cultures. The bioactivities and molecular mechanisms of lignans and neolignans obtained by biotechnological methods are further explored, including analyses of species distribution and molecular targets. Finally, the review discusses the advantages and limitations of different production platforms, challenges associated with industrial-scale production, and future perspectives for the sustainable and scalable development of lignan-based products.
- 11 July 2026
- Published by Taylor & Francis in Natural Product Research
- p. 1-5
An exploratory evaluation of the therapeutic potential of Parmentiera aculeata
1. Parmentiera aculeata (Kunth) Seem., commonly known as cuajilote, belongs to the Bignoniaceae family and is part of the native vegetation of Mexico. (Alvarez-Olivera et al., 2010) In traditional ...
- 11 July 2026
- Published by Taylor & Francis in Natural Product Research
- p. 1-5
An exploratory evaluation of the therapeutic potential of Parmentiera aculeata
1. Parmentiera aculeata (Kunth) Seem., commonly known as cuajilote, belongs to the Bignoniaceae family and is part of the native vegetation of Mexico. (Alvarez-Olivera et al., 2010) In traditional ...
- Open Access
- 22 July 2025
- Published by Elsevier in Journal of Agriculture and Food Research
- Vol. 23
Comparative analysis of the chemical composition and cytotoxic activity of broccoli by-products as an alternative source of bioactive compounds
- 22 July 2025
- Published by Elsevier in Journal of Agriculture and Food Research
- Vol. 23
Open AccessComparative analysis of the chemical composition and cytotoxic activity of broccoli by-products as an alternative source of bioactive compounds
- Open Access
Chemical Profiles and Nitric Oxide Inhibitory Activities of the Copal Resin and Its Volatile Fraction of Bursera bipinnata
Bursera bipinnata (DC.) Engl. (B. bipinnata), commonly known as “copal chino,” is a widely distributed Mexican tree found in transitional zones between pine-oak and deciduous forests. It is valued for its high-quality copal resin, traditionally used in ceremonies and offerings. Additionally, B. bipinnata is recognized for its significant value in traditional medicine, particularly in treating ailments associated with inflammation. In this work, the inhibition of nitric oxide (NO) production of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. In contrast, the volatile fraction exhibited 37.43 ± 7.13% inhibition at a concentration of 40 µg/mL. Chromatographic analyses of the total resin enabled the chemical characterization of eleven pentacyclic triterpenes belonging to the ursane, oleanane, and lupane series, as well as eight monoterpenes. Notably, the structures of compounds 15, 17, and 29–35 are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity observed for B. bipinnata resin in this study may be attributed to its high content of the triterpenes α-amyrin (15, 29.7%) and 3-epilupeol (17, 38.1%), both known for their anti-inflammatory properties. These findings support the traditional use of this copal resin.
Open AccessChemical Profiles and Nitric Oxide Inhibitory Activities of the Copal Resin and Its Volatile Fraction of Bursera bipinnata
Bursera bipinnata (DC.) Engl. (B. bipinnata), commonly known as “copal chino,” is a widely distributed Mexican tree found in transitional zones between pine-oak and deciduous forests. It is valued for its high-quality copal resin, traditionally used in ceremonies and offerings. Additionally, B. bipinnata is recognized for its significant value in traditional medicine, particularly in treating ailments associated with inflammation. In this work, the inhibition of nitric oxide (NO) production of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. In contrast, the volatile fraction exhibited 37.43 ± 7.13% inhibition at a concentration of 40 µg/mL. Chromatographic analyses of the total resin enabled the chemical characterization of eleven pentacyclic triterpenes belonging to the ursane, oleanane, and lupane series, as well as eight monoterpenes. Notably, the structures of compounds 15, 17, and 29–35 are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity observed for B. bipinnata resin in this study may be attributed to its high content of the triterpenes α-amyrin (15, 29.7%) and 3-epilupeol (17, 38.1%), both known for their anti-inflammatory properties. These findings support the traditional use of this copal resin.
- Open Access
- 4 June 2025
- Published by MDPI AG in Preprints.org
Chemical Profiles and Anti-Inflammatory Activities of the Copal Resin and Its Volatile Fraction of Bursera bipinnata
Bursera bipinnata is known as “copal chino, is a small tree that grows in steep areas and is part of the transitional populations of pine and oak forests and lowland deciduous forests. It is the taxon with the widest geographic distribution in México and considered a source of high-grade copal resin used in ceremonies and offerings. Also, B. bipinnata is considered to have great value in traditional medicine to treat ailments related to in-flammation. In this work, the anti-inflammatory effects of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. The resin extract was the best inhibitor with a 65.83 ± 8.53 % of inhibition of NO production with IC50 = 30 ± 3.3 µg/mL. In contrast, its volatile fraction showed a 37.43± 7.13 % of inhibition at 40 µg/mL. GC/MS and LC analysis of the total resin allowed the chemical characterization of eleven pentacyclic triterpenes with ursane, oleanane, and lupane skeletons, and eight monoterpenes. The structures of compounds (15, 17, 29-35) are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity of the most abundant constituents of the resin of B. bipinnata (α-amyrin (15), 3-epilupeol (17) and α-phellandrene (1) has been previously demonstrated which con-firms the activity showed by the resin as well as the traditional use of this important copal resin. The chemical profile of B. bippinata differs from that of other copal resins (e.g. B. copallifera) in the presence of a greater variety of triterpenes in the resin.
- 4 June 2025
- Published by MDPI AG in Preprints.org
Open AccessChemical Profiles and Anti-Inflammatory Activities of the Copal Resin and Its Volatile Fraction of Bursera bipinnata
Bursera bipinnata is known as “copal chino, is a small tree that grows in steep areas and is part of the transitional populations of pine and oak forests and lowland deciduous forests. It is the taxon with the widest geographic distribution in México and considered a source of high-grade copal resin used in ceremonies and offerings. Also, B. bipinnata is considered to have great value in traditional medicine to treat ailments related to in-flammation. In this work, the anti-inflammatory effects of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. The resin extract was the best inhibitor with a 65.83 ± 8.53 % of inhibition of NO production with IC50 = 30 ± 3.3 µg/mL. In contrast, its volatile fraction showed a 37.43± 7.13 % of inhibition at 40 µg/mL. GC/MS and LC analysis of the total resin allowed the chemical characterization of eleven pentacyclic triterpenes with ursane, oleanane, and lupane skeletons, and eight monoterpenes. The structures of compounds (15, 17, 29-35) are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity of the most abundant constituents of the resin of B. bipinnata (α-amyrin (15), 3-epilupeol (17) and α-phellandrene (1) has been previously demonstrated which con-firms the activity showed by the resin as well as the traditional use of this important copal resin. The chemical profile of B. bippinata differs from that of other copal resins (e.g. B. copallifera) in the presence of a greater variety of triterpenes in the resin.
- Open Access
- 13 March 2025
- Published by American Chemical Society (ACS) in ChemRxiv
Comparative Analysis of the Chemical Composition and Cytotoxic Activity of Broccoli By-products as a Source of Bioactive Compounds
Broccoli is one of the most widely consumed cruciferous vegetables worldwide; however, only about 30%—primarily the florets—are consumed, while the remaining parts are considered waste. In this study, we analyzed broccoli by-products from Mexican crops, specifically evaluating the ethanolic extracts of bagasse (BB) and residual leaves (BL) for their growth-inhibitory effects on PC-3, HeLa, and Hep3B cancer cell lines. Both BB and BL selectively inhibited cervical cancer cell proliferation by approximately 50%. A principal component analysis (PCA) of volatile compounds identified three main groups: fatty acids, methyl esters, sterols, and diterpenoids. Notably, sterols were the predominant components in the hexane fraction of broccoli bagasse (BB-H) (>90%), whereas fatty acids were the most abundant in the hexane fraction of broccoli leaves (BL-H) (>50%). Furthermore, two phytoalexins, caulilexin C (1) and 3-indoleacetonitrile (2), were isolated and characterized by NMR, exhibiting IC50 values of 23.43 and 33.65 μg/mL, respectively, against the HeLa cell line. Also, they showed desirable drug-like properties. These findings provide valuable insights into the chemical composition of broccoli by-products from Mexican crops, emphasizing their potential as a source of bioactive compounds with pharmaceutical and food applications.
- 13 March 2025
- Published by American Chemical Society (ACS) in ChemRxiv
Open AccessComparative Analysis of the Chemical Composition and Cytotoxic Activity of Broccoli By-products as a Source of Bioactive Compounds
Broccoli is one of the most widely consumed cruciferous vegetables worldwide; however, only about 30%—primarily the florets—are consumed, while the remaining parts are considered waste. In this study, we analyzed broccoli by-products from Mexican crops, specifically evaluating the ethanolic extracts of bagasse (BB) and residual leaves (BL) for their growth-inhibitory effects on PC-3, HeLa, and Hep3B cancer cell lines. Both BB and BL selectively inhibited cervical cancer cell proliferation by approximately 50%. A principal component analysis (PCA) of volatile compounds identified three main groups: fatty acids, methyl esters, sterols, and diterpenoids. Notably, sterols were the predominant components in the hexane fraction of broccoli bagasse (BB-H) (>90%), whereas fatty acids were the most abundant in the hexane fraction of broccoli leaves (BL-H) (>50%). Furthermore, two phytoalexins, caulilexin C (1) and 3-indoleacetonitrile (2), were isolated and characterized by NMR, exhibiting IC50 values of 23.43 and 33.65 μg/mL, respectively, against the HeLa cell line. Also, they showed desirable drug-like properties. These findings provide valuable insights into the chemical composition of broccoli by-products from Mexican crops, emphasizing their potential as a source of bioactive compounds with pharmaceutical and food applications.
- Open Access
- 2 March 2025
- Published by Wiley in ChemBioChem
- Vol. 26 (6) , e202400823
Reviewing Glycosyl‐Inositols: Natural Occurrence, Biological Roles, and Synthetic Techniques
Glycosyl‐inositols are molecules consisting of one or more α‐ or β‐D‐glycosyl residues bonded primarily to inositol or methyl‐inositol. These derivatives are found in plants, yeast, bacteria, and parasites, and exhibit diverse biological properties. The limited availability of glycosyl inositols from natural sources has led to significant interest in chemical and enzymatic synthesis techniques due to their potential applications in various fields. This review provides a comprehensive overview of inositols, methyl‐inositols, and primarily glycosyl inositols, focusing on their classification, natural occurrence, biological roles, and potential applications across different disciplines. Inositols, particularly myo‐inositol and its derivatives are widely distributed in plants and play essential roles in biochemical processes and metabolic functions in different organs and tissues. Glycosyl inositols, including glycosylphosphatidylinositols, glycosyl inositol phosphorylceramides, phosphatidylinositol mannosides, monoglycosyl and diglycosyl derivatives, are discussed, emphasizing their structural diversity and biological functions. Methods for their chemical and enzymatic synthesis are also reviewed, highlighting recent advances and challenges in the field. Overall, this comprehensive review underscores the significance of glycosyl inositols as versatile molecules with diverse biological functions and promising applications in scientific research and industry.
- 2 March 2025
- Published by Wiley in ChemBioChem
- Vol. 26 (6) , e202400823
Open AccessReviewing Glycosyl‐Inositols: Natural Occurrence, Biological Roles, and Synthetic Techniques
Glycosyl‐inositols are molecules consisting of one or more α‐ or β‐D‐glycosyl residues bonded primarily to inositol or methyl‐inositol. These derivatives are found in plants, yeast, bacteria, and parasites, and exhibit diverse biological properties. The limited availability of glycosyl inositols from natural sources has led to significant interest in chemical and enzymatic synthesis techniques due to their potential applications in various fields. This review provides a comprehensive overview of inositols, methyl‐inositols, and primarily glycosyl inositols, focusing on their classification, natural occurrence, biological roles, and potential applications across different disciplines. Inositols, particularly myo‐inositol and its derivatives are widely distributed in plants and play essential roles in biochemical processes and metabolic functions in different organs and tissues. Glycosyl inositols, including glycosylphosphatidylinositols, glycosyl inositol phosphorylceramides, phosphatidylinositol mannosides, monoglycosyl and diglycosyl derivatives, are discussed, emphasizing their structural diversity and biological functions. Methods for their chemical and enzymatic synthesis are also reviewed, highlighting recent advances and challenges in the field. Overall, this comprehensive review underscores the significance of glycosyl inositols as versatile molecules with diverse biological functions and promising applications in scientific research and industry.
- Open Access
- 5 January 2025
- Published by Elsevier in Carbohydrate Polymers
- Vol. 352, 123236
Branching and molecular weight in levan: A detailed analysis of structural variability and enzymatic hydrolysis susceptibility
- 5 January 2025
- Published by Elsevier in Carbohydrate Polymers
- Vol. 352, 123236
Open AccessBranching and molecular weight in levan: A detailed analysis of structural variability and enzymatic hydrolysis susceptibility
- Open Access
Finding a Novel Chalcone–Cinnamic Acid Chimeric Compound with Antiproliferative Activity against MCF-7 Cell Line Using a Free-Wilson Type Approach
In this work, we carried out the design and synthesis of new chimeric compounds from the natural cytotoxic chalcone 2′,4′-dihydroxychalcone (2′,4′-DHC, A) in combination with cinnamic acids. For this purpose, a descriptive and predictive quantitative structure–activity relationship (QSAR) model was developed to study the chimeric compounds’ anti-cancer activities against human breast cancer MCF-7, relying on the presence or absence of structural motifs in the chalcone structure, like in a Free-Wilson approach. For this, we used 207 chalcone derivatives with a great variety of structural modifications over the α and β rings, such as halogens (F, Cl, and Br), heterocyclic rings (piperazine, piperidine, pyridine, etc.), and hydroxyl and methoxy groups. The multilinear equation was obtained by the genetic algorithm technique, using logIC50 as a dependent variable and molecular descriptors (constitutional, topological, functional group count, atom-centered fragments, and molecular properties) as independent variables, with acceptable statistical parameter values ( = 86.93, LMO = 82.578, BOOT = 80.436, and EXT = 80.226), which supports the predictive ability of the model. Considering the aromatic and planar nature of the chalcone and cinnamic acid cores, a structural-specific QSAR model was developed by incorporating geometrical descriptors into the previous general QSAR model, again, with acceptable parameters ( = 85.554, LMO = 80.534, BOOT = 78.186, and EXT = 79.41). Employing this new QSAR model over the natural parent chalcone 2′,4′-DHC (A) and the chimeric compound 2′-hydroxy,4′-cinnamate chalcone (B), the predicted cytotoxic activity was achieved with values of 55.95 and 17.86 µM, respectively. Therefore, to corroborate the predicted cytotoxic activity compounds A and B were synthesized by two- and three-step reactions. The structures were confirmed by 1H and 13C NMR and ESI+MS analysis and further evaluated in vitro against HepG2, Hep3B (liver), A-549 (lung), MCF-7 (breast), and CasKi (cervical) human cancer cell lines. The results showed IC50 values of 11.89, 10.27, 56.75, 14.86, and 29.72 µM, respectively, for the chimeric cinnamate chalcone B. Finally, we employed B as a molecular scaffold for the generation of cinnamate candidates (C–K), which incorporated structural motifs that enhance the cytotoxic activity (pyridine ring, halogens, and methoxy groups) according to our QSAR model. ADME/tox in silico analysis showed that the synthesized compounds A and B, as well as the proposed chalcones C and G, are the best candidates with adequate drug-likeness properties. From all these results, we propose B (as a molecular scaffold) and our two QSAR models as reliable tools for the generation of anti-cancer compounds over the MCF-7 cell line.Open AccessFinding a Novel Chalcone–Cinnamic Acid Chimeric Compound with Antiproliferative Activity against MCF-7 Cell Line Using a Free-Wilson Type Approach
In this work, we carried out the design and synthesis of new chimeric compounds from the natural cytotoxic chalcone 2′,4′-dihydroxychalcone (2′,4′-DHC, A) in combination with cinnamic acids. For this purpose, a descriptive and predictive quantitative structure–activity relationship (QSAR) model was developed to study the chimeric compounds’ anti-cancer activities against human breast cancer MCF-7, relying on the presence or absence of structural motifs in the chalcone structure, like in a Free-Wilson approach. For this, we used 207 chalcone derivatives with a great variety of structural modifications over the α and β rings, such as halogens (F, Cl, and Br), heterocyclic rings (piperazine, piperidine, pyridine, etc.), and hydroxyl and methoxy groups. The multilinear equation was obtained by the genetic algorithm technique, using logIC50 as a dependent variable and molecular descriptors (constitutional, topological, functional group count, atom-centered fragments, and molecular properties) as independent variables, with acceptable statistical parameter values ( = 86.93, LMO = 82.578, BOOT = 80.436, and EXT = 80.226), which supports the predictive ability of the model. Considering the aromatic and planar nature of the chalcone and cinnamic acid cores, a structural-specific QSAR model was developed by incorporating geometrical descriptors into the previous general QSAR model, again, with acceptable parameters ( = 85.554, LMO = 80.534, BOOT = 78.186, and EXT = 79.41). Employing this new QSAR model over the natural parent chalcone 2′,4′-DHC (A) and the chimeric compound 2′-hydroxy,4′-cinnamate chalcone (B), the predicted cytotoxic activity was achieved with values of 55.95 and 17.86 µM, respectively. Therefore, to corroborate the predicted cytotoxic activity compounds A and B were synthesized by two- and three-step reactions. The structures were confirmed by 1H and 13C NMR and ESI+MS analysis and further evaluated in vitro against HepG2, Hep3B (liver), A-549 (lung), MCF-7 (breast), and CasKi (cervical) human cancer cell lines. The results showed IC50 values of 11.89, 10.27, 56.75, 14.86, and 29.72 µM, respectively, for the chimeric cinnamate chalcone B. Finally, we employed B as a molecular scaffold for the generation of cinnamate candidates (C–K), which incorporated structural motifs that enhance the cytotoxic activity (pyridine ring, halogens, and methoxy groups) according to our QSAR model. ADME/tox in silico analysis showed that the synthesized compounds A and B, as well as the proposed chalcones C and G, are the best candidates with adequate drug-likeness properties. From all these results, we propose B (as a molecular scaffold) and our two QSAR models as reliable tools for the generation of anti-cancer compounds over the MCF-7 cell line.