Article
Biochemistry & Molecular Biology
Maria Argirova, Maya Guncheva, Georgi Momekov, Emiliya Cherneva, Rositsa Mihaylova, Miroslav Rangelov, Nadezhda Todorova, Petko Denev, Kameliya Anichina, Anelia Mavrova, Denitsa Yancheva
Summary: Designed 1H-benzimidazol-2-yl hydrazones with hydroxy and methoxy phenyl moieties elongated the nucleation phase and slowed down tubulin polymerization in vitro. The compounds showed marked antineoplastic activity in low concentrations against MCF-7 and AR-230 cell lines. Some derivatives exhibited high ability to scavenge peroxyl radicals comparable to well-known phenolic antioxidants. The compounds hold promise as new agents with combined antioxidant and antineoplastic action.
Article
Chemistry, Medicinal
Anja Bec, Lucija Hok, Leentje Persoons, Els Vanstreels, Dirk Daelemans, Robert Vianello, Marijana Hranjec
Summary: The study prepared a series of novel acrylonitrile compounds using different synthesis methods, showing strong anti-proliferative activity against malignant tumor cells with good selectivity towards normal cells. The compounds were also tested for their inhibition of tubulin polymerization in vitro, revealing a potential mechanism of action for their biological activity.
Article
Chemistry, Medicinal
N. Perin, L. Hok, A. Bec, L. Persoons, E. Vanstreels, D. Daelemans, R. Vianello, M. Hranjec
Summary: In this study, novel N-substituted benzimidazole-based acrylonitriles were designed, synthesized, and evaluated for their antiproliferative activity. The N,N-dimethylamino substituted acrylonitriles exhibited strong and selective antiproliferative activity with low toxicity. Mechanism of action studies revealed that the most active compounds inhibited tubulin polymerization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ryad M. Noha, Mohammed K. Abdelhameid, M. Mohsen Ismail, Manal R. Mohammed, Elmeligie Salwa
Summary: A series of benzimidazole derivatives with methoxylated aryl groups were designed and synthesized as potential cytotoxic agents. Some compounds showed strong inhibitory activity on tumor cells in vitro and had effects on key processes such as cell cycle and apoptosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Md Jahangir Alam, Ozair Alam, Ahmad Perwez, Moshahid Alam Rizvi, Mohd Javed Naim, Vegi Naidu, Mohd Imran, Mohammed M. Ghoneim, Sultan Alshehri, Faiyaz Shakeel
Summary: In this study, a series of compounds were designed, synthesized, and evaluated for their anti-cancer activity and cytotoxicity. Compound 5o showed excellent cytotoxicity and most of the compounds exhibited drug-like properties.
Article
Chemistry, Physical
K. Veena, M. S. Raghu, K. Yogesh Kumar, C. B. Pradeep Kumar, Fahad A. Alharti, M. K. Prashanth, Byong-Hun Jeon
Summary: This study successfully developed a new class of benzimidazole-linked thiazole compounds as chemotherapeutic drugs with anti-tuberculosis activity. Some of these compounds showed high antimicrobial effects against drug-resistant Mycobacterium tuberculosis strains. The study also revealed some structure-activity relationships and demonstrated the interaction of the compounds with the key protein MmpL3 through molecular docking studies. In addition, the potential drug properties of these compounds were validated through in-silico predictions.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Physical
Yuqian Bai, Yang Hou, Qiuchan Wang, Chang Lu, Xuce Ma, Zishi Wang, Hongliang Xu
Summary: Monilinia fructicola can cause economic losses by infesting plants during fruit flowering and storage and transportation. The increase in resistance to methyl benzimidazole carbamates (MBCs) fungicides is a growing concern. We studied the changes in binding mode between four MBCs fungicides and wild type and mutant Monilinia fructicola beta-tubulin protein. By constructing homology related models and using molecular docking and dynamics simulations, we identified the optimal binding mode for benomyl, carbendazim, thiabendazole, and thiophanate-methyl with Monilinia fructicola beta-tubulin protein. The resistance mechanism of M. fructicola beta-tubulin protein to MBCs fungicides and cross-resistance mechanisms were elucidated through computer simulation.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Medicine, Research & Experimental
In-ho Song, Su Jeong Park, Gyu Seong Yeom, Keum-soo Song, Taisun Kim, Satish Balasaheb Nimse
Summary: In recent years, there has been significant interest in developing microtubule-targeting agents (MTAs) as novel small-molecule anticancer drugs. Most research on benzimidazole scaffold-based MTAs has focused on developing microtubule-destabilizing agents, with little focus on microtubule-stabilizing agents. In this study, benzimidazole derivatives NI-11 and NI-18 were found to exhibit profound anticancer activity as microtubule-stabilization agents. They showed higher selectivity indexes compared to currently available anticancer agents, inhibited cancer cell motility and migration, and induced early phase apoptosis. The compounds also upregulated DeY-alpha-tubulin expression and downregulated Ac-a-tubulin expression in cancer cells, indicating their microtubule-stabilizing activity.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Sravani Sana, Velma Ganga Reddy, T. Srinivasa Reddy, Ramya Tokala, Rahul Kumar, Suresh K. Bhargava, Nagula Shankaraiah
Summary: The study introduces a novel class of compounds with moderate to interesting cytotoxicity against various cancer cell lines, with compound 18i showing the highest potency and specificity towards A549 (lung cancer) cells. Flow cytometry analysis revealed that 18i induced G2/M phase cell cycle arrest, indicating potential anticancer activity. The most active compound, 18i, demonstrated enhanced microtubule disruption and significant antitumor effects through multiple mechanisms, including apoptosis induction, ROS generation, and inhibition of cellular migration.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Ulviye Acar Cevik, Aysen Isik, Ravikumar Kapavarapu, Kaan Kucukoglu, Hayrunnisa Nadaroglu, Hayrani Eren Bostanci, Yusuf Ozkay, Zafer Asim Kaplancikli
Summary: In this study, a series of benzimidazole-triazole derivatives were synthesized and evaluated for their inhibitory activity against hCA-I and hCA-II. These compounds displayed good inhibitory activities against both enzymes, with compound 6j being the most active. The cytotoxic effects of compounds 6a-6k on normal cells were also assessed, and non-competitive enzyme inhibition kinetics were observed. Molecular docking studies confirmed the binding interactions between compound 6j and the enzyme's active site, supporting the experimental findings.
JOURNAL OF MOLECULAR STRUCTURE
(2024)
Article
Chemistry, Medicinal
Muhammad Khattab, Ahmed A. Al-Karmalawy
Summary: The study investigated the binding interactions and electronic configurations of nine benzimidazole-based anthelmintics against the tubulin protein as a cancer target. Results showed that flubendazole had the highest binding affinity with tubulin protein compared to other drugs, suggesting its potential as a promising anticancer candidate.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Shankaraiah Ambala, Vishnu Thumma, Veerabhadraiah Mallikanti, Shalini Aitha, Raghavender Matta, Jalapathi Pochampally
Summary: New benzimidazole-based piperazine analogues (9 a-n) were synthesized and screened for their cytotoxicity against human breast cancer cell lines MCF-7 and MDA-MB-231. Compound 9 f showed outstanding activity against both cell lines, and compound 9 m exhibited superior activity against MDA-MB-231 cells. Compound 9 c showed activity on par with Doxorubicin against MCF-7 cells. The active compounds did not show any toxicity on MCF-10A cells and exhibited notable binding energies and interactions with Cyclin-dependent kinase 6.
Article
Biochemistry & Molecular Biology
Kameliya Anichina, Maria Argirova, Rumyana Tzoneva, Veselina Uzunova, Anelia Mavrova, Dimitar Vuchev, Galya Popova-Daskalova, Filip Fratev, Maya Guncheva, Denitsa Yancheva
Summary: The synthesized benzimidazole derivatives exhibited strong anthelmintic activity against Trichinella spiralis and modulated microtubule polymerization, suggesting a close relationship between the two. In vitro cytotoxicity tests showed low to moderate cytotoxic effects.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Lingyu Shi, Shanbo Yang, Jing Chang, Yujing Zhang, Wenjing Liu, Jun Zeng, Jingsen Meng, Renshuai Zhang, Chao Wang, Dongming Xing
Summary: A series of new compounds were synthesized and evaluated for their antitumor activity as tubulin polymerization inhibitors. Compound 7k showed the strongest anti-proliferative activity and could block the cell cycle and induce apoptosis.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Dilep Kumar Sigalapalli, Gaddam Kiranmai, G. Parimala Devi, Ramya Tokala, Sravani Sana, Chaturvedula Tripura, Govinda Shivaji Jadhav, Manasa Kadagathur, Nagula Shankaraiah, Narayana Nagesh, Bathini Nagendra Babu, Neelima D. Tangellamudi
Summary: A new series of imidazo[1,2-a]pyridine-oxadiazole hybrids were synthesized and evaluated for their anticancer activity, with compound 6d showing the highest potency against lung cancer cells. Compound 6d induced apoptosis and inhibited tubulin polymerization in A549 cells, displaying effective binding with CT-DNA and alpha/beta-tubulin receptor.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Physical
Kritika Laxmikeshav, Ambati Himaja, Nagula Shankaraiah
Summary: This article reviews the research progress and synthetic strategies of benzimidazole molecules as tubulin polymerisation modulators in medicinal chemistry. By evaluating the structure-activity relationships, it provides valuable references for the study and development of cytotoxic agents.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Review
Medicine, Research & Experimental
Janice Jacson Mandumpala, Stephin Baby, Antriya Annie Tom, Chandraiah Godugu, Nagula Shankaraiah
Summary: Triple-negative breast cancer (TNBC) is a highly lethal subtype of breast cancer with limited treatment options due to its complexity, drug resistance, and lack of therapeutic targets. Recent studies have shown the importance of epigenetic regulation in TNBC development, with a focus on histone methyltransferases and histone demethylases as potential targets for new targeted therapies in TNBC treatment.
Article
Biochemistry & Molecular Biology
Jay Prakash Soni, G. Nikitha Reddy, Ziaur Rahman, Anamika Sharma, Akella Spandana, Regur Phanindranath, Manoj P. Dandekar, Narayana Nagesh, Nagula Shankaraiah
Summary: In this study, a series of new beta-carboline tethered indole-3-glyoxylamide derivatives were synthesized, which showed significant pharmacological properties and prominent cytotoxicity. The compounds exhibited remarkable cytotoxicity against human cancer cell lines, especially melanoma, and showed selective toxicity towards cancer cells compared to normal cells. The compounds induced apoptosis and showed potential as DNA binders and inhibitors of Topoisomerase II. Molecular modeling studies confirmed their excellent DNA intercalation potential. In addition, in silico analysis predicted the promising drug-like properties of the synthesized derivatives.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Kritika Laxmikeshav, Pooja Sharma, Manisurya Palepu, Pravesh Sharma, Ashutosh Mahale, Joel George, Regur Phanindranath, Manoj P. Dandekar, Onkar Prakash Kulkarni, Narayana Nagesh, Nagula Shankaraiah
Summary: A new series of carboxamide-bearing benzimidazole derivatives have been investigated for their cytotoxicity on selected human tumor cells. Compounds 10g and 10m showed selective cytotoxicity towards SK-Mel-28 skin cancer cells and were safe for human non-cancerous lung epithelial cells.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Stephy Elza John, Anamika Sharma, Shivani Gulati, Darshana Bora, Nagula Shankaraiah
Summary: In modern medicinal chemistry, a molecular hybridization approach was used to design and synthesize a new class of cis-stilbene-based 1,2,4-triazole/1,3,4-oxadiazole conjugates. These conjugates exhibited promising cytotoxicity against selected human cancer cell lines, with cis-stilbene-based 1,2,4-triazole conjugate 5a being the most effective against the A549 cell line. Mechanistic analysis revealed that 5a induced apoptosis, DNA damage, nuclear morphological changes, and ROS generation, and exhibited G2/M phase arrest and tubulin polymerization inhibition. Additionally, 5a showed no toxicity towards normal cells and demonstrated significant anti-cancer activity.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kritika Laxmikeshav, Mone Sayali, Geetanjali Devabattula, Durgesh G. G. Valapil, Ashutosh Mahale, Pravesh Sharma, Joel George, Regur Phanindranath, Chandraiah Godugu, Onkar P. P. Kulkarni, Narayana Nagesh, Nagula Shankaraiah
Summary: A simple click protocol was used to synthesize 1,2,3-triazole-linked benzimidazoles as potential anticancer agents, which showed significant cytotoxicity against SK-Mel-28 cancer cells and no cytotoxicity against normal BEAS-2B cells. Compound 12j inhibited cellular migration, colony formation, and induced apoptosis in SK-Mel-28 cells.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Kiira M. Ratia, Zhengnan Shen, Jesse Gordon-Blake, Hyun Lee, Megan S. Laham, Isabella S. Krider, Nicholas Christie, Martha Ackerman-Berrier, Christopher Penton, Natalie G. Knowles, Soumya Reddy Musku, Jiqiang Fu, Ganga Reddy Velma, Rui Xiong, Gregory R. J. Thatcher
Summary: In aging and disease, NAD+ is depleted by catabolism to NAM. NAD+ supplementation is being pursued for human health benefits. Activation of NAMPT, the rate-limiting step in NAD+ biosynthesis, can increase NAM salvage. N-PAMs were discovered as novel NAMPT activators, with a mechanism of action involving the regulation of NAMPT turnover through the rear channel.
Article
Biochemistry & Molecular Biology
Ramulu Parupalli, Ravikumar Akunuri, Akella Spandana, Regur Phanindranath, Suneela Pyreddy, Mohd Rabi Bazaz, Manasa Vadakattu, Swanand Vinayak Joshi, Sushmitha Bujji, Balakishan Gorre, Venkata Madhavi Yaddanapudi, Manoj P. Dandekar, Velma Ganga Reddy, Narayana Nagesh, Srinivas Nanduri
Summary: Cancer is characterized by uncontrolled cell proliferation and the invasion of neighboring tissues and organs. DNA has emerged as a promising therapeutic target for cancer due to its crucial role in cell division and maintenance. In this study, a series of compounds were synthesized and evaluated for their anticancer activity against human cancer cell lines. Several compounds showed strong inhibitory effects on HeLa cells, with selectivity over non-cancerous cells. The compounds induced cell cycle arrest, apoptosis, and DNA damage in HeLa cells, suggesting their potential as anticancer agents.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Darshana Bora, Anamika Sharma, Stephy Elza John, Nagula Shankaraiah
Summary: A series of new combretastatin-oxindole derivatives were synthesized using (E)-bis(phenyl) acrylohydrazides and substituted isatins. The cytotoxic activity of these derivatives was evaluated against various cancer cell lines, and compound 9o showed potent anti-cancer activity against lung cancer cells. It induced changes in nuclear morphology and apoptosis, inhibited tubulin polymerization, and had a binding interaction with the 3E22 protein.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Akash P. Sakla, Biswajit Panda, Ashutosh Mahale, Pravesh Sharma, Kritika Laxmikeshav, Mursalim Ali Khan, Onkar Prakash Kulkarni, Chandraiah Godugu, Nagula Shankaraiah
Summary: In this study, regiospecific nucleophilic ring-opening of spiroaziridine oxindoles was performed to synthesize 3-substituted-thiooxindole derivatives as anticancer agents. Among the new compounds, 7d and 9c showed promising cytotoxic activity against HCT-116 cells with IC50 values of 6.73 ± 0.36 and 6.64 ± 0.95 μM, respectively. Further studies demonstrated significant alterations in nuclear and morphological characteristics, loss of mitochondrial membrane potential, and cell cycle arrest in G2-M phase for compound 9c. In addition, compound 9c exhibited tubulin polymerase inhibition with an IC50 value of 9.73 ± 0.18 μM, supported by docking interactions with tubulin.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Sravani Sana, Srinivas Reddy Dannarm, Ramya Tokala, Sowmya Dastari, Manda Sathish, Rahul Kumar, Rajesh Sonti, Nagula Shankaraiah
Summary: A sustainable synthetic protocol for the construction of color-tunable fluorescent molecules has been achieved via ruthenium-catalyzed multiple C-H activation/annulation. The strategy provides easy access to a library of fused heterocyclic frameworks with significant yields. A systematic investigation of photophysical properties has also been conducted for the discovery of new fluorophores.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Sravani Sana, Sowmya Dastari, Dannarm Srinivas Reddy, Ramya Tokala, Manda Sathish, Rajesh Sonti, Nagula Shankaraiah
Summary: A sustainable protocol using a photoredox-mediated dual catalytic copper/ruthenium system has been developed for the construction of unsymmetrical diarylamines. This approach allows for the easy access to medicinally relevant amines by sequentially arylating ammonia with various (hetero)aryl bromides. The resulting mono-arylated amines can undergo a copper-mediated cross-coupling with aryl boronic acids, enabling the synthesis of the tyrosine kinase inhibitor Imatinib in an eco-friendly manner.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Yellaiah Tangella, Jay Prakash Soni, Nagula Shankaraiah, Diana Abril, Manda Sathish
Summary: A versatile and efficient one-pot protocol has been developed for the synthesis of amides from easily accessible carboxylic acids and amines by employing trimethylsilyl azide as a promoter at room temperature. This reaction proceeds via an in situ generated acyl azide intermediates followed by the nucleophilic substitution of amines. Notably, most of the desired amides were obtained by simple filtration in excellent yields. The significant advantages like metal-free mild reaction conditions, higher yields, easily removable volatile byproducts, operational simplicity, and broad substrate scope make the transformation a useful contribution for the synthesis of biologically important amides.
Article
Biochemistry & Molecular Biology
Jay Prakash Soni, Shrilekha Chilvery, Anamika Sharma, G. Nikitha Reddy, Chandraiah Godugu, Nagula Shankaraiah
Summary: A series of 2-((3-(indol-3-yl)-pyrazol-5-yl)imino)thiazolidin-4-ones were designed and synthesized as potential and effective chemotherapeutic agents. Compound 6c exhibited the highest cytotoxicity against melanoma cancer cells and showed selectivity towards cancer cells. It induced early-stage apoptosis, arrested cell-cycle in the G2/M phase, and inhibited tubulin polymerization. Molecular modeling studies confirmed its stable binding to tubulin and interactions with active pocket residues.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Darshana Bora, Khan Mehtab Samir, Anamika Sharma, Shrilekha Chilvery, Sapana Bansod, Stephy Elza John, Mursalim Ali Khan, Chandraiah Godugu, Nagula Shankaraiah
Summary: In this study, a new series of cis-stilbene-1,2,3-triazole congeners were synthesized and evaluated for their potential anticancer and tubulin polymerization inhibition activity. The most active compound, 9j, showed selective cytotoxicity against colorectal cancer cells and induced apoptotic cell death. It also inhibited tubulin polymerization and exhibited G2/M phase cell cycle arrest.
RSC MEDICINAL CHEMISTRY
(2023)