M Shahar Yar
@jamiahamdard.edu
Professor, Pharmaceutical Chemistry
Jamia Hamdard
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Organic Chemistry, Drug Discovery, Pharmaceutical Science
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Aman Kumar Mahto, Kanupriya, Shalini Kumari, Mohammad Shahar Yar, and Rikeshwer Prasad Dewangan
Elsevier BV
Sonakshi Tyagi, Salahuddin Salahuddin S, Avijit Mazumder, Rajnish Kumar, Vimal Datt, Shabana Km Shabana, Abhishek Shankar Sharma, Mohamed Jawed Ahsan, and Mohammad Shahar Yar
EManuscript Technologies
Km Shabana, Salahuddin, Avijit Mazumder, Rajnish Kumar, Vimal Datt, Sonakshi Tyagi, Mohammad Shahar Yar, Mohamed Jawed Ahsan, and Mohammad Sarafroz
Bentham Science Publishers Ltd.
Background: Benzimidazole (Benz-fused bicyclic ring system) is the most versatile class of heterocyclic compounds due to its numerous applications in industrial and synthetic organic chemistry because of its many biological actions. Benzimidazole analogs have been used to discover various medical problems, such as cancer, bacterial infections, fungi infections, etc. Researchers are studying nitrogencontaining hybrid heterocyclic compounds because they provide a broad range of therapeutic potential and have minimal side effects. Objective: The current literature review emphasizes recent developments in the design of new benzimidazole derivatives as possible anticancer agents with their relationship between structure and activity, which will give insight into the future design of more active benzimidazole molecules. Results: The present review consists of synthetic protocols for the synthesis of benzimidazole derivatives along with their pharmacological potentials and structure-activity relationship in correlation with synthetic molecules to provide a depth view of the work done on benzimidazole. Conclusion: It would be significant for further research in developing better drug molecules representing a potent derivative of medicinal agents.
Pushkar Kumar Ray, Salahuddin, Avijit Mazumder, Rajnish Kumar, Mohamed Jawed Ahsan, and Mohamed Shahar Yar
Bentham Science Publishers Ltd.
Background: Pyrazoline is a heterocyclic compound with five members, two nitrogen atoms in a circle, and one endocyclic bond. Pyrazoline is a popular electron-rich nitrogen carrier that combines exciting electronic properties with the potential for dynamic applications. Pyrazine derivatives have been synthesized using a variety of methods, all of which have shown to have a strong biological effect. Objective: The study of the biological activity of pyrazoline derivatives has been a fascinating field of pharmaceutical chemistry. Pyrazolines are used in a wide range of applications. The pyrazoline derivatives described in the literature between 2000 and 2021 were the focus of this study. Pyazolines have been discussed in terms of their introduction, general synthetic method, and anticancer potential in the current review. Conclusion: Pyrazolines are well-known heterocyclic compounds. Pyrazoline is a five-membered ring containing three carbon and two nitrogen atoms nearby. The synthesis of pyrazolines has been described using a variety of methods. Anticancer activity has been discovered in a number of pyrazoline derivatives, which encourages further research. The use of pyrazoline to treat cancer has piqued researchers' interest in learning more about this moiety.
Noorul Hasan, Saima Zameer, Abul Kalam Najmi, Suhel Parvez, Mohammad Shahar Yar, and Mohd Akhtar
Springer Science and Business Media LLC
Sagar Joshi, Salahuddin, Avijit Mazumder, Rajnish Kumar, Km Shabana, Sonakshi Tyagi, Kavita Rana, Mohamed Jawed Ahsan, Mohammad Shahar Yar, Arvind Arya,et al.
Bentham Science Publishers Ltd.
Background: Piperine is a natural compound found in black pepper that has been traditionally used for various therapeutic purposes. In the ayurvedic system of medication there is a lot of evidence which shows that the piperine is widely used for different therapeutic purpose. In recent years, there has been an increasing interest in the pharmacological and therapeutic potential of piperine and its derivatives in modern medicine. In order to increase the bioavailability and therapeutic effectiveness of piperine and its analogs, researchers have been looking at various extraction methods and synthesis approaches. Many studies have been conducted in this area because of the promise of piperine as a natural substitute for synthetic medications. Objectives: The objective of this review article is to provide an up-to-date analysis of the literature on the synthesis of piperine analogs, including their extraction techniques and various biological activities such as antihypertensive, antidiabetic, insecticidal, antimicrobial, and antibiotic effects. Additionally, the review aims to discuss the potential of piperine in modern medicine, given its traditional use in various medicinal systems such as Ayurveda, Siddha, and Unani. The article also provides a comprehensive analysis of the plant from which piperine is derived. Conclusion: This review article provides a thorough examination of piperine and the source plant. The best extraction technique for the extraction of piperine and the synthesis of its analogs with various biological activities, including antihypertensive, antidiabetic, insecticidal, antibacterial, and antibiotic properties, are covered in the article. This review aims to provide an updated analysis of the literature on the synthesis of piperine analogs.
Salahuddin, Sonakshi Tyagi, Avijit Mazumder, Rajnish Kumar, Vimal Datt, Km Shabana, Mohammad Shahar Yar, and Mohamed Jawed Ahsan
Bentham Science Publishers Ltd.
Abstract: Quinoline has recently become an important heterocyclic molecule due to its numerous industrial and synthetic organic chemistry applications. Quinoline derivatives have been used in clinical trials for a variety of medical conditions that causes cancer. The present literature study is composed of recent progress (mainly from 2010 to the present) in the production of novel quinoline derivatives as potential anti-cancer agents, as well as their structure-activity relationship, which will provide insight into the development of more active quinoline hybrids in the future. : The present review comprises the synthetic protocols of biologically active Quinoline analogs with their structure-activity relationship studies as anti-cancer agents, which provide depth view of work done on quinoline derivatives to the medicinal chemist for future research.
Salahuddin, Abhishek Shankar Sharma, Avijit Mazumder, Rajnish Kumar, Vimal Datt, Km Shabana, Sonakshi Tyagi, Mohammad Shahar Yar, and Mohamed Jawed Ahsan
Bentham Science Publishers Ltd.
Abstract: Due to their diverse applications in industrial and synthetic organic chemistry, quinoline and 1,3,4-oxadiazole have become important heterocyclic compounds. Quinoline and 1,3,4- oxadiazole compounds have been developed for various medical conditions such as anti-cancer, anti-bacterial, anti-fungal, antimalarial, antioxidants, anti-HIV, anticonvulsant, antiviral, etc. The current review includes synthetic protocols for biologically active 1,3,4-oxadiazole incorporating quinoline hybrids with their structure-activity relationship to explore work (Mainly from 2010 to 2021) based on 1,3,4-oxadiazole-quinoline hybrids to the medicinal chemist for further research in the development of the molecule.
Pushkar Kumar Ray, Salahuddin Salahuddin, Avijit Mazumder, Rajnish Kumar, Mohamed Jawed Ahsan, and Mohammad Shahar Yar
EManuscript Technologies
Prasanna A. Yakkala, Samir R. Panda, Syed Shafi, V. G. M. Naidu, M. Shahar Yar, Philemon N. Ubanako, Samson A. Adeyemi, Pradeep Kumar, Yahya E. Choonara, Eugene V. Radchenko,et al.
MDPI AG
A series of new 1,2,4-triazolo-linked bis-indolyl conjugates (15a–r) were prepared by multistep synthesis and evaluated for their cytotoxic activity against various human cancer cell lines. It was observed that they were more susceptible to colon and breast cancer cells. Conjugates 15o (IC50 = 2.04 μM) and 15r (IC50 = 0.85 μM) illustrated promising cytotoxicity compared to 5-fluorouracil (5-FU, IC50 = 5.31 μM) against the HT-29 cell line. Interestingly, 15o and 15r induced cell cycle arrest at the G0/G1 phase and disrupted the mitochondrial membrane potential. Moreover, these conjugates led to apoptosis in HT-29 at 2 μM and 1 μM, respectively, and also enhanced the total ROS production as well as the mitochondrial-generated ROS. Immunofluorescence and Western blot assays revealed that these conjugates reduced the expression levels of the PI3K-P85, β-catenin, TAB-182, β-actin, AXIN-2, and NF-κB markers that are involved in the β-catenin pathway of colorectal cancer. The results of the in silico docking studies of 15r and 15o further support their dual inhibitory behaviour against PI3K and tankyrase. Interestingly, the conjugates have adequate ADME-toxicity parameters based on the calculated results of the molecular dynamic simulations, as we found that these inhibitors (15r) influenced the conformational flexibility of the 4OA7 and 3L54 proteins.
Kashif Haider, Shivani Sharma, Yuba Raj Pokharel, Subham Das, Alex Joseph, Abul Kalam Najmi, Faiz Ahmad, and Mohammad Shahar Yar
Wiley
AbstractWe herein report a new series of indole‐tethered pyrazoline derivatives as potent anticancer agents. A total of 12 compounds were designed and synthesized by conventional as well as microwave‐irradiated synthesis methods. The latter method results in a significant reduction in the duration of reaction along with improved yields. All synthesized derivatives (7a−7l) were evaluated for their cytotoxic activity against A431, HeLa, and MDAMB‐231 cell lines. Compounds 7a and 7b were found most potent in the series and demonstrated an IC50 value of 3.17 and 5.16 µM against the A431 cell line, respectively, compared to the standard drug doxorubicin. Compounds 7a and 7b significantly suppress colony formation, migration, and S phase cell cycle arrest of A431 cells. Furthermore, compound 7a regulated the expression of apoptotic proteins causing the downregulation of procaspase 3/9, antiapoptotic protein Bcl‐xL, and upregulation of proapoptotic protein Bax in a dose‐dependent manner. Topoisomerase enzyme inhibition assay confirmed that compounds 7a and 7b can significantly inhibit topoisomerase IIα. In vivo oral acute toxicity of compounds 7a and 7b revealed that both compounds are safe compared to doxorubicin; cardiomyopathy studies showed normal architecture of cardiomyocytes and myofibrils. In addition, molecular docking studies revealed the possible interaction of compounds 7a and 7b within the active binding site of the topoisomerase enzyme. The 100 ns molecular dynamic simulation of compounds 7a and 7b proved that both compounds validate all screening parameters.
F. Deeba, M. Shahar Yar, Mohammad Rafi Haidar, ArunK. Sharma and Manju Sharma
Objective(s): CB1 antagonism arbitrates a dormant shape to the endocannabinoid system that alleviates diverse pathological incidents of diabesity. The present study pursued the synthesis and evaluation of thiazolidine derivative (BAC) having pleiotropic action on CB1R, with or without AM251 (selective antagonist of the CB1 receptor) against high-fat diet (HFD) induced diabesity in C57BL/6 mice. Materials and Methods: A molecular docking study for CB1 antagonistic potential was conducted by Maestro 11.4 program (Schrodinger Inc., USA), and the thiazolidine derivative BAC was synthesized. The assessment of varied parameters including anthropometric, neurobehavioral, hyperglycemia, dyslipidemia, oxidative stress, and inflammatory cytokines was evaluated in HFD-fed animals as compared with individual and combined treatments of BAC and AM251. Results: Incomparable to AM251, the treatment of BAC was reported for a significant reduction in food intake and obesity, diabetic biomarkers, lipid profile, oxidative stress, and proinflammatory cytokine release. Moreover, the BAC treatment showed no significant alteration in neurobehavioral activity, including anxiety and depression. Conclusion: The preliminary in silico study suggests that BAC has a close interaction with CB1 antagonism but has no sign of neurobehavioral alteration. Simultaneously, this compound showed significant ability to ameliorate diversity by the underlying mechanisms of minimizing oxidative stress, regularizing the lipid profile, and reducing pro-inflammatory cytokines.
Kashif Haider, Mohd Shafeeque, Shaikh Yahya, and M. Shahar Yar
Elsevier BV
Kashif Haider, Subham Das, Alex Joseph, and M. Shahar Yar
Wiley
AbstractCancer is one of the leading causes of death. Globally a huge number of deaths and new incidences are reported annually. Heterocyclic compounds have been proved to be very effective in the treatment of different types of cancer. Among different heterocyclic scaffolds, quinazoline and quinazolinone core were found versatile and interesting with many biological activities. In the discovery of novel anticancer agents, the Quinazoline core is very effective. The FDA has approved more than 20 drugs as an anticancer bearing quinazoline or quinazolinone core in the last two decades. One prime example is Dacomitinib, which was newly approved for non‐small‐cell lung carcinoma treatment in 2018. These drugs work by different pathways to prevent the spread of cancer cell progression, including inhibition of different kinases, tubulin, kinesin spindle protein, and so forth. This review presented recent developments of quinazoline/quinazolinone scaffold bearing derivatives as anticancer agents acting as epidermal growth factor receptor (EGFR) vascular endothelial growth factor receptor (VEGFR), and dual EGFR/VEGFR inhibitors.
Gourav Grover, Rohit Pal, Rohit Bhatia, M. Shahar Yar, Rajarshi Nath, Shamsher Singh, Khadga Raj, Bhupinder Kumar, and Md Jawaid Akhtar
Springer Science and Business Media LLC
Bharti Chauhan, Rajnish Kumar, Salahuddin, Himanshu Singh, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Mohd Mustaqeem Abdullah, Mohammad Shahar Yar, Mohamed Jawed Ahsan, Neeraj Kumar,et al.
American Chemical Society (ACS)
In the presented manuscript, a new series of 2-[4-methoxy-3-(5-substituted phenyl-[1,3,4]oxadiazol-2-ylmethoxy)-phenyl]-benzothiazoles (6a–n) have been synthesized and studied in vivo and in silico for their anticonvulsant potential. Maximum electroshocks (MES) and subcutaneous pentylenetetrazol (scPTZ) models have been used for in vivo anticonvulsant activity. Auto Dock 4.2 software was used for in silico studies, and the targeted protein was 5IOV.sThe antidepressant activity of selected compounds (most active) was determined as a reduction in locomotor activity through an actophotometer. In vivo and In silico studies proved that among all the synthesized compounds, 6f, 6h, 6j, and 6l were the most potent with no neurotoxicity as compared to conventional drugs (phenytoin and phenobarbital). The in silico studies also indicated about different binding interactions of synthetic compounds to localize the binding receptors. The most likely mode of action for these drugs, according to the docking analysis of active compounds with various targets, is their binding to the VGCC and NMDA receptors.
Ali Sartaj, Annu, Meraj Alam, Largee Biswas, Mohammad Shahar Yar, Showkat Rasool Mir, Anita Kamra Verma, Sanjula Baboota, and Javed Ali
Informa UK Limited
Abstract Purpose The current research investigated the development and evaluation of dual drug-loaded nanostructure lipidic carriers (NLCs) of green tea extract and Ribociclib. Method In silico study were performed to determine the effectiveness of combinational approach. The prepared NLCs were subjected to in vitro drug release, lipolysis, haemolysis and cell line studies to assess their in vivo prospect. Results In silico study was done to get docking score of EGCG (−8.98) close to Ribociclib (−10.78) in CDK-4 receptors. The prepared NLCs exhibited particle size (175.80 ± 3.51 nm); PDI (0.571 ± 0.012); and %EE [RBO (80.91 ± 1.66%) and GTE 75.98 ± 2.35%)] respectively. MCF-7 cell lines were used to evaluate the MTT assay, cellular uptake and antioxidant (ROS and SOD) of prepared NLCs. In vitro drug release showed the controlled release up to 72 h. In vitro lipolysis and in vitro haemolysis studies showed the availability of drugs at absorption sites and the greater in vivo prospects of NLCs respectively. Pharmacokinetic study revealed a 3.63-fold and 1.53-fold increment in RBO and GTE bioavailability in female Wistar rats respectively. Conclusion The prominent potential of green tea extract and RBO-loaded NLCs in enhancing their therapeutic efficacy for better treatment of breast cancer.
Kashif Haider, Anku Sharma, M Shahar Yar, Prasanna Anjaneyulu Yakkala, Syed Shafi, and Ahmed Kamal
Informa UK Limited
ABSTRACT Introduction Hyperactivated RAS signaling is reported in 13% of all human cancers, in which ~80% resulted due to KRAS mutations alone. Direct inhibition of KRAS is an important aspect in treating KRAS-related tumors. Despite the efforts of more than four decades, not many KRAS inhibitors have been successful in obtaining clinical approval, except the very recent FDA approval for sotorasib. In recent years, the understanding of structural insights and allosteric pocket identification at catalytic sites of KRAS are likely to provide an excellent opportunity for the development of much more effective clinical candidates. Area covered The presented review article mainly summarizes the developments of small molecule KRAS inhibitors as drug candidates and rational approaches that are being utilized for the selective targeting of KRAS signaling in the mutant cancer cells. Expert opinion After the initial success in targeting the mutant KRAS G12C variants, the search has been shifted to address the challenges concerning the resistance and efficacy of small molecule KRAS inhibitors. However, the contribution of other KRAS mutations at G12V, G13C, and G13D variants causing cancers is much higher than the mutations at G12C. In view of this aspect, specific attention is required to target all other mutations as well. Accordingly, for the development of KRAS targeted therapies, the design of small molecule inhibitors that can inhibit KRAS signaling and as well as target inhibition of other signaling pathways like RAS-SOS and RAS-PI3K has to be explored extensively.
Kashif Haider, Sara Rehman, Ankita Pathak, Abul K. Najmi, and Mohammad S. Yar
Wiley
AbstractTargeted therapy plays a pivotal role in cancer therapeutics by countering the drawbacks of conventional treatment like adverse events and drug resistance. Over the last decade, heterocyclic derivatives have received considerable attention as cytotoxic agents by modulating various signaling pathways. Benzothiazole is an important heterocyclic scaffold that has been explored for its therapeutic potential. Benzothiazole‐based derivatives have emerged as potent inhibitors of enzymes such as EGFR, VEGFR, PI3K, topoisomerases, and thymidylate kinases. Several researchers have designed, synthesized, and evaluated benzothiazole scaffold‐based enzyme inhibitors. Of these, several inhibitors have entered various phases of clinical trials. This review describes the recent advances and developments of benzothiazole architecture‐based derivatives as potent anticancer agents.
Afreen, Salahuddin, Avijit Mazumder, Sagar Joshi, Rajnish Kumar, Mohammad Shahar Yar, and Mohamed Jawed Ahsan
Bentham Science Publishers Ltd.
Currently, black pepper commands the leading position among all the spices as a spice of great commercial importance in all the world trade and finds its way into the dietary habits of millions of people worldwide. Black pepper is biologically known as Piper nigrum and contains piperine as the main active chemical constituent. This paper highlights various general methods for extracting piperine from the crude drug such as maceration extraction, hydrotropic extraction, accelerated solvent extraction, thin-layer chromatography, and extraction with ethanol & dichloromethane Ionic fluid-based ultrasonic-assisted extraction, etc. In this review, piperine and its analogs exhibit numerous pharmacological activities and synthetic schemes of insecticidal activity, anti-cancer activity, anti-inflammatory activity, anti-diabetic activity, anti-hyperlipidemic activity, antifungal activity, narcotic activity, etc. and its structure-activity relationship. The biochemistry of piperine has also been summarized in the presented article. This very exhaustive review details the complete information about piperine, its derivatives, and further processing. Furthermore, the current study summarises recent research that has linked piperine to its use as a treatment for a variety of ailments.
Noorul Hasan, Saima Zameer, Abul Kalam Najmi, Suhel Parvez, Mohammad Shahar Yar, and Mohd Akhtar
Springer Science and Business Media LLC